HCSGD entry for MYC
1. General information
| Official gene symbol | MYC |
|---|---|
| Entrez ID | 4609 |
| Gene full name | v-myc myelocytomatosis viral oncogene homolog (avian) |
| Other gene symbols | MRTL bHLHe39 c-Myc |
| Links to Entrez Gene | Links to Entrez Gene |
2. Neighbors in the network
3. Gene ontology annotation
GO ID | GO term | Evidence | Category |
|---|---|---|---|
| GO:0000122 | Negative regulation of transcription from RNA polymerase II promoter | IDA | biological_process |
| GO:0000165 | MAPK cascade | IMP | biological_process |
| GO:0001658 | Branching involved in ureteric bud morphogenesis | ISS | biological_process |
| GO:0002053 | Positive regulation of mesenchymal cell proliferation | ISS | biological_process |
| GO:0003677 | DNA binding | ISS TAS | molecular_function |
| GO:0003700 | Sequence-specific DNA binding transcription factor activity | IDA IEA | molecular_function |
| GO:0005515 | Protein binding | IPI | molecular_function |
| GO:0005634 | Nucleus | IDA IEA | cellular_component |
| GO:0005654 | Nucleoplasm | IDA TAS | cellular_component |
| GO:0005730 | Nucleolus | IDA | cellular_component |
| GO:0006112 | Energy reserve metabolic process | NAS | biological_process |
| GO:0006338 | Chromatin remodeling | IDA | biological_process |
| GO:0006351 | Transcription, DNA-templated | TAS | biological_process |
| GO:0006367 | Transcription initiation from RNA polymerase II promoter | TAS | biological_process |
| GO:0006879 | Cellular iron ion homeostasis | IDA | biological_process |
| GO:0006974 | Cellular response to DNA damage stimulus | IDA | biological_process |
| GO:0007050 | Cell cycle arrest | IDA | biological_process |
| GO:0007179 | Transforming growth factor beta receptor signaling pathway | TAS | biological_process |
| GO:0007219 | Notch signaling pathway | TAS | biological_process |
| GO:0008134 | Transcription factor binding | IPI | molecular_function |
| GO:0008284 | Positive regulation of cell proliferation | IDA | biological_process |
| GO:0010332 | Response to gamma radiation | IDA | biological_process |
| GO:0010467 | Gene expression | TAS | biological_process |
| GO:0015671 | Oxygen transport | NAS | biological_process |
| GO:0032204 | Regulation of telomere maintenance | IMP | biological_process |
| GO:0032403 | Protein complex binding | IDA | molecular_function |
| GO:0032873 | Negative regulation of stress-activated MAPK cascade | ISS | biological_process |
| GO:0034644 | Cellular response to UV | IEP | biological_process |
| GO:0035690 | Cellular response to drug | IDA | biological_process |
| GO:0042493 | Response to drug | IEP | biological_process |
| GO:0043066 | Negative regulation of apoptotic process | ISS | biological_process |
| GO:0043234 | Protein complex | IDA | cellular_component |
| GO:0043280 | Positive regulation of cysteine-type endopeptidase activity involved in apoptotic process | IDA | biological_process |
| GO:0044346 | Fibroblast apoptotic process | TAS | biological_process |
| GO:0045656 | Negative regulation of monocyte differentiation | IMP | biological_process |
| GO:0045893 | Positive regulation of transcription, DNA-templated | IDA | biological_process |
| GO:0045944 | Positive regulation of transcription from RNA polymerase II promoter | IMP TAS | biological_process |
| GO:0046983 | Protein dimerization activity | IEA | molecular_function |
| GO:0048146 | Positive regulation of fibroblast proliferation | IDA IMP | biological_process |
| GO:0048147 | Negative regulation of fibroblast proliferation | IDA | biological_process |
| GO:0050679 | Positive regulation of epithelial cell proliferation | IDA | biological_process |
| GO:0051276 | Chromosome organization | IDA | biological_process |
| GO:0051782 | Negative regulation of cell division | IDA | biological_process |
| GO:0060070 | Canonical Wnt signaling pathway | IDA | biological_process |
| GO:0070491 | Repressing transcription factor binding | IPI | molecular_function |
| GO:0070848 | Response to growth factor | TAS | biological_process |
| GO:0070888 | E-box binding | IDA | molecular_function |
| GO:0090096 | Positive regulation of metanephric cap mesenchymal cell proliferation | ISS | biological_process |
| GO:2000573 | Positive regulation of DNA biosynthetic process | IMP | biological_process |
| GO:2001022 | Positive regulation of response to DNA damage stimulus | IDA | biological_process |
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4. Expression levels in datasets
- Meta-analysis result
| p-value up | p-value down | FDR up | FDR down |
|---|---|---|---|
| 0.0089647848 | 0.0199467080 | 0.2422090164 | 0.2748718472 |
- Individual experiment result
( "-" represent NA in the specific microarray platform )
( "-" represent NA in the specific microarray platform )
| Data source | Up or down | Log fold change |
|---|---|---|
| GSE11954 | Down | -1.9395008572 |
| GSE13712_SHEAR | Up | 0.8816459326 |
| GSE13712_STATIC | Up | 0.4413682396 |
| GSE19018 | Down | -0.0361935493 |
| GSE19899_A1 | Up | 1.2531120048 |
| GSE19899_A2 | Up | 1.3916921396 |
| PubMed_21979375_A1 | Up | 1.8275710873 |
| PubMed_21979375_A2 | Up | 1.3814136747 |
| GSE35957 | Down | -0.5517237280 |
| GSE36640 | Down | -1.3021940866 |
| GSE54402 | Up | 0.6193730316 |
| GSE9593 | Up | 0.2202121451 |
| GSE43922 | Up | 0.7978531715 |
| GSE24585 | Down | -1.6858445498 |
| GSE37065 | Down | -0.6395422676 |
| GSE28863_A1 | Up | 0.0011836768 |
| GSE28863_A2 | Up | 0.1056139550 |
| GSE28863_A3 | Up | 0.4799363742 |
| GSE28863_A4 | Down | -0.4346419352 |
| GSE48662 | Down | -0.8153273843 |
5. Regulation relationships with compounds/drugs/microRNAs
- Compounds
Not regulated by compounds
- Drugs
Name | Drug | Accession number |
|---|---|---|
| Nadroparin | DB08813 | - |
- MicroRNAs
- mirTarBase
- mirTarBase
MiRNA_name | mirBase ID | miRTarBase ID | Experiment | Support type | References (Pubmed ID) |
|---|---|---|---|---|---|
| hsa-miR-24-3p | MIMAT0000080 | MIRT000121 | Luciferase reporter assay//Microarray//qRT-PCR//Western blot//Reporter assay;qRT-PCR;Microarray;Other | Functional MTI | 19748357 |
| hsa-let-7a-5p | MIMAT0000062 | MIRT000417 | Western blot | Functional MTI | 20033209 |
| hsa-let-7a-5p | MIMAT0000062 | MIRT000417 | qRT-PCR | Functional MTI (Weak) | 17942906 |
| hsa-let-7a-5p | MIMAT0000062 | MIRT000417 | qRT-PCR//Western blot | Functional MTI | 16651716 |
| hsa-let-7g-5p | MIMAT0000414 | MIRT000475 | qRT-PCR//Luciferase reporter assay//Western blot//Western blot;qRT-PCR;Other | Functional MTI | 20309945 |
| hsa-let-7g-5p | MIMAT0000414 | MIRT000475 | qRT-PCR | Non-Functional MTI (Weak) | 21618519 |
| hsa-miR-451a | MIMAT0001631 | MIRT006358 | Luciferase reporter assay | Functional MTI | 21464222 |
| hsa-miR-34a-5p | MIMAT0000255 | MIRT000695 | Luciferase reporter assay//Western blot//Reporter assay;Western blot;qRT-PCR;Microarray;Other | Functional MTI | 19696787 |
| hsa-miR-34a-5p | MIMAT0000255 | MIRT000695 | Luciferase reporter assay//qRT-PCR//Western blot | Functional MTI | 21294122 |
| hsa-miR-34a-5p | MIMAT0000255 | MIRT000695 | Luciferase reporter assay | Functional MTI | 22159222 |
| hsa-miR-34a-5p | MIMAT0000255 | MIRT000695 | Sequencing | Functional MTI (Weak) | 20371350 |
| hsa-miR-98-5p | MIMAT0000096 | MIRT003438 | Luciferase reporter assay//Northern blot//qRT-PCR//ChIP | Functional MTI | 19528081 |
| hsa-miR-98-5p | MIMAT0000096 | MIRT003438 | qRT-PCR | Functional MTI (Weak) | 17942906 |
| hsa-miR-98-5p | MIMAT0000096 | MIRT003438 | Microarray | Functional MTI (Weak) | 19088304 |
| hsa-let-7c-5p | MIMAT0000064 | MIRT003748 | Luciferase reporter assay//Northern blot//Western blot | Functional MTI | 17877811 |
| hsa-miR-26a-5p | MIMAT0000082 | MIRT003968 | Western blot | Non-Functional MTI | 19524505 |
| hsa-miR-145-5p | MIMAT0000437 | MIRT004290 | qRT-PCR//Luciferase reporter assay//Western blot | Functional MTI | 19202062 |
| hsa-miR-145-5p | MIMAT0000437 | MIRT004290 | Luciferase reporter assay//qRT-PCR//Western blot | Functional MTI | 21092188 |
| hsa-miR-21-5p | MIMAT0000076 | MIRT004307 | Northern blot//qRT-PCR//ChIP | Functional MTI (Weak) | 19528081 |
| hsa-miR-34b-5p | MIMAT0000685 | MIRT004401 | Luciferase reporter assay | Functional MTI | 19461653 |
| hsa-miR-34c-5p | MIMAT0000686 | MIRT004402 | Luciferase reporter assay | Functional MTI | 19461653 |
| hsa-miR-17-5p | MIMAT0000070 | MIRT005288 | Western blot | Functional MTI | 18695042 |
| hsa-miR-17-5p | MIMAT0000070 | MIRT005288 | CLASH | Functional MTI (Weak) | 23622248 |
| hsa-miR-20a-5p | MIMAT0000075 | MIRT005289 | Western blot | Functional MTI | 18695042 |
| hsa-miR-34b-3p | MIMAT0004676 | MIRT005319 | Luciferase reporter assay//Western blot | Functional MTI | 18768788 |
| hsa-miR-34b-3p | MIMAT0004676 | MIRT005319 | Immunohistochemistry//qRT-PCR | Functional MTI (Weak) | 18802929 |
| hsa-miR-378a-3p | MIMAT0000732 | MIRT005482 | Immunoblot//Luciferase reporter assay//qRT-PCR | Functional MTI | 21242960 |
| hsa-miR-135a-5p | MIMAT0000428 | MIRT007105 | Luciferase reporter assay//Western blot | Functional MTI | 23176581 |
| hsa-miR-449c-5p | MIMAT0010251 | MIRT007308 | Luciferase reporter assay | Functional MTI | 23507140 |
| hsa-miR-429 | MIMAT0001536 | MIRT016647 | Reporter assay;Western blot;Other | Functional MTI | 21684154 |
| hsa-miR-335-5p | MIMAT0000765 | MIRT017925 | Microarray | Functional MTI (Weak) | 18185580 |
| hsa-miR-335-5p | MIMAT0000765 | MIRT017925 | Western blot | Functional MTI | 21618216 |
| hsa-let-7f-5p | MIMAT0000067 | MIRT032089 | qRT-PCR | Functional MTI (Weak) | 19956384 |
| hsa-miR-320b | MIMAT0005792 | MIRT036232 | CLASH | Functional MTI (Weak) | 23622248 |
| hsa-miR-744-5p | MIMAT0004945 | MIRT037690 | CLASH | Functional MTI (Weak) | 23622248 |
| hsa-miR-423-5p | MIMAT0004748 | MIRT038140 | CLASH | Functional MTI (Weak) | 23622248 |
| hsa-miR-320a | MIMAT0000510 | MIRT044759 | CLASH | Functional MTI (Weak) | 23622248 |
| hsa-let-7b-5p | MIMAT0000063 | MIRT052217 | CLASH | Functional MTI (Weak) | 23622248 |
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- mirRecord
- mirRecord
MicroRNA name | mirBase ID | Target site number | MiRNA mature ID | Test method inter | MiRNA regulation site | Reporter target site | Pubmed ID |
|---|---|---|---|---|---|---|---|
| hsa-miR-145-5p | MIMAT0000437 | 1 | hsa-miR-145 | {Immunostaining} | {overexpression by miRNA precursor transfection} | 19202062 | |
| hsa-miR-34c-5p | MIMAT0000686 | NA | hsa-miR-34c-5p | {Western blot} | {overexpression by miRNA mimics tranfection} | 20212154 | |
| hsa-miR-34a-5p | MIMAT0000255 | NA | hsa-miR-34a | {Western blot} | {overexpression by miRNA mimics tranfection} | 20212154 | |
| hsa-miR-24-3p | MIMAT0000080 | 1 | hsa-miR-24 | {Western blot} | {overexpression by miRNA mimics tranfection} | 19748357 | |
| hsa-miR-24-3p | MIMAT0000080 | 2 | hsa-miR-24 | {Western blot} | {overexpression by miRNA mimics tranfection} | 19748357 | |
| hsa-miR-24-3p | MIMAT0000080 | 3 | hsa-miR-24 | {Western blot} | {overexpression by miRNA mimics tranfection} | 19748357 | |
| hsa-miR-24-3p | MIMAT0000080 | 5 | hsa-miR-24 | {Western blot} | {overexpression by miRNA mimics tranfection} | 19748357 | |
| hsa-miR-24-3p | MIMAT0000080 | 6 | hsa-miR-24 | {Western blot} | {overexpression by miRNA mimics tranfection} | 19748357 | |
| hsa-miR-24-3p | MIMAT0000080 | 4 | hsa-miR-24 | {Western blot} | {overexpression by miRNA mimics tranfection} | 19748357 |
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6. Text-mining results about the gene
Gene occurances in abstracts of cellular senescence-associated articles: 110 abstracts the gene occurs.
PubMed ID of the article | Sentenece the gene occurs |
|---|---|
| 27362652 | Targets of miR-34 miRNAs, including E2F1, c-Myc, and cyclin E2, were lower in IPF type II AECs |
| 27349249 | To explore the role of HPV oncoproteins on OSM expression, the expression of HPV16E6 in the HCK1T Tet-On condition was induced by doxycycline and HPV16E6 was found to significantly upregulate levels of OSM mRNA and protein, with concomitant upregulation of c-Myc |
| 27297181 | Notably, Tert expression increased colony formation of induced pluripotent stem (iPS) cells after the introduction of four reprogramming factors, Oct-4, klf4, SOX-2, and c-Myc into the transgenic fibroblasts |
| 27294914 | In addition, ginsenoside Rg1 decreased beta-catenin and c-Myc mRNA expression and enhanced the phosphorylation of GSK-3beta |
| 26798365 | However, the expression of senescence-related gene, p21, and oncogene, c-Myc, was significantly upregulated in the late phase, which had close relations with the obviously increased cell senescence |
| 26571381 | GSE4 expression also activated c-myc and TERT promoters and increase of c-myc, TERT and TERC expression |
| 26571381 | Mutation of the Aspartic Acid residue that is conserved in the pseudouridine synthase domain present in GSE4 did not impair its activity, except for the repression of c-myc promoter activity and the decrease of c-myc, TERT and TERC gene expression in dyskerin-mutated cells |
| 26529363 | Suppression of RAD21 Induces Senescence of MDA-MB-231 Human Breast Cancer Cells Through RB1 Pathway Activation Via c-Myc Downregulation |
| 26529363 | Further biochemical analyses revealed that RAD21 knockdown led to the downregulation of c-Myc and its targets, including CDK4, a negative regulator of RB1, and blockedRB1 phosphorylation (pRB1), and the RB1-mediated transcriptional repression of E2F |
| 26529363 | Moreover, c-Myc downregulation was partially mediated by proteasome-dependent degradation within promyelocytic leukemia (PML) nuclear bodies, which were found to be highly abundant during RAD21 knockdown-induced senescence |
| 26529363 | Exogenous c-Myc reconstitution rescued cells from RAD21 silencing-induced senescence |
| 26529363 | Altogether, data arising from this study implicate a novel function of RAD21 in cellular senescence in MDA-MB-231 cells that is mainly dependent onRB1 pathway activation via c-Myc downregulation |
| 26477312 | In addition to the activation of oncogenes c-MYC and STAT3 in tumor cells, a number of cytokines and growth factors, such as IL1beta, IL6 and SPP1 (osteopontin, a key biomarker for PCa), were upregulated in NFATc1-induced PCa, establishing a tumorigenic microenvironment involving both NFATc1 positive and negative cells for prostate tumorigenesis |
| 26412380 | We have found evidence suggesting that ARF and p53 are essential for tumor regression upon MYC inactivation through distinct mechanisms ARF through p53-independent affect, is required to for MYC to regulate the expression of genes that are required for both the induction of cellular senescence as well as recruitment of innate immune activation |
| 26412380 | We have found evidence suggesting that ARF and p53 are essential for tumor regression upon MYC inactivation through distinct mechanisms ARF through p53-independent affect, is required to for MYC to regulate the expression of genes that are required for both the induction of cellular senescence as well as recruitment of innate immune activation |
| 26236688 | MOE(HIGH) had enhanced protein expression of c-myc, Cyclin E, p53, and FOXM1 with reduced expression of p21 |
| 26096152 | Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSC) by the forced expression of the transcription factors OCT4, SOX2, KLF4 and c-MYC |
| 25988535 | It was found that these ruthenium(II) complexes exhibited considerable in vitro anticancer activities and that they were the effective stabilizers of telomeric and G-quadruplex-DNA (G4-DNA) in promoter of c-myc, which acted as a telomerase inhibitor targeting G4-DNA and induced cell senescence and apoptosis |
| 25937285 | These phenotypes were mediated by a coordinated suppression of p53 and upregulation of c-MYC downstream of ATM inactivation |
| 25873431 | Acidified bile acids increase hTERT expression via c-myc activation in human gastric cancer cells |
| 25873431 | We report here that bile acids under acidified media increase hTERT expression via c-myc activation in primary human gastric cancer cell lines |
| 25873431 | Human gastric cancer MKN28, MGC803 and SGC7901 cells were treated with 100 microM deoxycholic acid (DCA) or chenodeoxycholic acid (CDCA) with or without acidified media in the presence or absence of the c-myc inhibitor 10058-F4 for 24 h |
| 25873431 | Similarly, the mRNA and protein levels of c-myc were also increased by bile acids in acidified media but not at a pH of 7 |
| 25873431 | Importantly, pharmacologic inhibition of c-myc using 10058-F4 prevented hTERT induction by DCA or CDCA in gastric cancer cells under acidic conditions |
| 25873431 | Bile acids (DCA and CDCA) under acidic conditions increased hTERT expression in human gastric cancer cells by activation of c-myc transcription |
| 25784651 | Addiction to MYC is a consequence of both cell-autonomous mechanisms, such as proliferative arrest, cellular senescence, and apoptosis, as well as non-cell autonomous mechanisms, such as shutdown of angiogenesis, and recruitment of immune effectors |
| 25784651 | Here, we show, using transgenic mouse models of MYC-induced T-ALL, that the loss of either p19ARF or p53 abrogates the ability of MYC inactivation to induce sustained tumor regression |
| 25784651 | Loss of p53 or p19ARF, influenced the ability of MYC inactivation to elicit the shutdown of angiogenesis; however the loss of p19ARF, but not p53, impeded cellular senescence, as measured by SA-beta-galactosidase staining, increased expression of p16INK4A, and specific histone modifications |
| 25784651 | Moreover, comparative gene expression analysis suggested that a multitude of genes involved in the innate immune response were expressed in p19ARF wild-type, but not null, tumors upon MYC inactivation |
| 25749381 | CSIG promotes hepatocellular carcinoma proliferation by activating c-MYC expression |
| 25749381 | Finally, CSIG protein directly interacted with c-MYC protein and increased c-MYC protein levels; the ubiquitination and degradation of c-MYC protein was increased with knockdown of CSIG |
| 25749381 | CSIG could also increase the expression of c-MYC protein in SMMC7721 cells in vivo, and it was noted that the level of c-MYC protein was also elevated in most human cancerous tissues with high level of CSIG |
| 25686834 | We discovered that miR-34a potently targeted c-Myc and FoxM1, both of which were involved in the activation of telomerase reverse transcriptase (hTERT) transcription, essential for the sustaining activity of telomerase to avoid senescence |
| 25593054 | Mechanistically, NS induction correlates with Pim-1 kinase-mediated stabilization of c-Myc |
| 25540416 | EBNA2 and EBNALP associate with EBV and cell enhancers, up-regulate the EBNA promoter, MYC, and EBV Latent infection Membrane Proteins (LMPs), which up-regulate BCL2 to protect EBV-infected B-cells from MYC proliferation-induced cell death |
| 25540416 | EBNA3A was at MYC, CDKN2A/B, CCND2, CXCL9/10, and BCL2, together with RUNX3, BATF, IRF4, and SPI1 |
| 25515777 | The acquisition of pluripotent cells can be achieved by combined overexpression of transcription factors Oct4, Klf4, Sox2 and c-Myc in somatic cells |
| 25435281 | Here, we addressed the above-mentioned open questions by multifaceted comparative analyses of human cellular models with inducible expression of c-Myc and H-RasV12 (Ras), two commonly deregulated oncoproteins operating in a functionally connected signaling network |
| 25089198 | In particular, CD4(+) helper T cells were shown to be essential to the mechanism by which MYC or BCR-ABL inactivation elicits "oncogene withdrawal |
| 25078983 | The protein levels of telomerase reverse transcriptase (TERT), UCP2, Akt, phosphor (p)-Akt, c-myc, and p53 were assessed by immunoblot |
| 25078983 | LY294002 pre-treatment significantly alleviated Ang II-induced HUVEC senescence, and partly reversed the elevation of TERT, UCP2, p-Akt, c-myc and p53 protein levels |
| 25077541 | We demonstrate that miR-17 targets both ADCY5 and IRS1, upregulating the downstream signals MKP7, FoxO3, LC3B, and HIF1alpha, and downregulating mTOR, c-myc, cyclin D1, and JNK |
| 25000517 | FOXO3a potentiates hTERT gene expression by activating c-MYC and extends the replicative life-span of human fibroblast |
| 25000517 | In addition, we found that FOXO3a binds to the novel binding element in the c-MYC promoter, and this interaction activates the transcription of the c-MYC gene |
| 25000517 | The resulting increase in c-MYC leads to higher levels of c-MYC recruited to the hTERT promoter and, in turn, activates hTERT gene expression |
| 24970385 | 5-aza-2'-deoxycytidine-mediated c-myc Down-regulation triggers telomere-dependent senescence by regulating human telomerase reverse transcriptase in chronic myeloid leukemia |
| 24970385 | Altogether, our results reveal the role of c-myc in telomere-dependent DAC-induced senescence and therefore provide new clues for improving chronic human leukemia treatments |
| 24934810 | MYC synergizes with activated BRAFV600E in mouse lung tumor development by suppressing senescence |
| 24934810 | MYC is a key factor in suppression of RAS/BRAF(V600E)-induced senescence in vitro |
| 24934810 | However, it is still unclear whether MYC has the same role during tumor development in vivo |
| 24934810 | Using a conditional, compound knock-in model of Cre-activated BRAF(V600E) and tamoxifen-regulatable MycER, we show that tamoxifen-induced activation of MYC accelerated the onset and increased the number and size of BRAF(V600E)-driven adenomas in a dose-dependent manner, resulting in reduced survival |
| 24934810 | Furthermore, MYC activation leads to reduced expression of the senescence markers p16(INK4A), p21(CIP1), and H3K9me3-containing heterochromatin foci, and an increased percentage of Ki67(+) tumor cells |
| 24934810 | This suggests that MYC already early during tumor formation suppresses a BRAF(V600E)-induced senescence-like state |
| 24934810 | Initial activation of MYC followed by tamoxifen withdrawal still resulted in an increased number of tumors and reduced survival |
| 24934810 | However, these tumors were of smaller size, showed increased expression of p16(INK4A) and p21(CIP1), and reduced number of Ki67(+) cells, indicating that MYC inactivation restores BRAF(V600E)-induced senescence |
| 24934810 | This suggests that senescence suppression by MYC is a discrete step in tumor development important for sustained tumor growth but preceding malignant transformation and that additional oncogenic events are required for carcinoma development and metastasis |
| 24890832 | MYC activation is a hallmark of cancer initiation and maintenance |
| 24890832 | The MYC proto-oncogene has been implicated in the pathogenesis of most types of human tumors |
| 24890832 | MYC activation alone in many normal cells is restrained from causing tumorigenesis through multiple genetic and epigenetically controlled checkpoint mechanisms, including proliferative arrest, apoptosis, and cellular senescence |
| 24890832 | When pathologically activated in a permissive epigenetic and/or genetic context, MYC bypasses these mechanisms, enforcing many of the "hallmark" features of cancer, including relentless tumor growth associated with DNA replication and transcription, cellular proliferation and growth, protein synthesis, and altered cellular metabolism |
| 24890832 | MYC mandates tumor cell fate, by inducing stemness and blocking cellular senescence and differentiation |
| 24890832 | Additionally, MYC orchestrates changes in the tumor microenvironment, including the activation of angiogenesis and suppression of the host immune response |
| 24890832 | Provocatively, brief or even partial suppression of MYC back to its physiological levels of activation can result in the restoration of intrinsic checkpoint mechanisms, resulting in acute and sustained tumor regression, associated with tumor cells undergoing proliferative arrest, differentiation, senescence, and apoptosis, as well as remodeling of the tumor microenvironment, recruitment of an immune response, and shutdown of angiogenesis |
| 24890832 | Hence, tumors appear to be "addicted" to MYC because of both tumor cell-intrinsic, cell-autonomous and host-dependent, immune cell-dependent mechanisms |
| 24890832 | Both the trajectory and persistence of many human cancers require sustained MYC activation |
| 24890832 | Multiscale mathematical modeling may be useful to predict when tumors will be addicted to MYC |
| 24890832 | MYC is a hallmark molecular feature of both the initiation and maintenance of tumorigenesis |
| 24853424 | Consistent with this observation, WIF1 caused a reduction in the expression of pluripotency and stemness markers (OCT4 and c-MYC), as well as adult stem cell self-renewal and multi-lineage differentiation markers, such as WNT3A, TCF4, c-KIT and MYB |
| 24729935 | Studies have identified alterations in the level or activity of factors such as SIRT1, PGC-1alpha, HIF-1alpha and c-MYC involved in key regulatory processes in the maintenance of mitochondrial structural integrity, biogenesis and function |
| 24645771 | Inactivation of MYC reverses tumorigenesis |
| 24645771 | The MYC proto-oncogene is an essential regulator of many normal biological programmes |
| 24645771 | MYC, when activated as an oncogene, has been implicated in the pathogenesis of most types of human cancers |
| 24645771 | MYC overexpression in normal cells is restrained from causing cancer through multiple genetically and epigenetically controlled checkpoint mechanisms, including proliferative arrest, apoptosis and cellular senescence |
| 24645771 | When pathologically activated in the correct epigenetic and genetic contexts, MYC bypasses these mechanisms and drives many of the 'hallmark' features of cancer, including uncontrolled tumour growth associated with DNA replication and transcription, cellular proliferation and growth, protein synthesis and altered cellular metabolism |
| 24645771 | MYC also dictates tumour cell fate by enforcing self-renewal and by abrogating cellular senescence and differentiation programmes |
| 24645771 | Moreover, MYC influences the tumour microenvironment, including activating angiogenesis and suppressing the host immune response |
| 24645771 | Provocatively, brief or even partial suppression of MYC back to its physiological levels of activation can lead to the restoration of intrinsic checkpoint mechanisms, resulting in acute and sustained tumour regression associated with tumour cells undergoing proliferative arrest, differentiation, senescence and apoptosis, as well as remodelling of the tumour microenvironment, recruitment of an immune response and shutdown of angiogenesis |
| 24645771 | Hence, tumours appear to be addicted to the MYC oncogene because of both tumour cell intrinsic and host-dependent mechanisms |
| 24645771 | MYC is important for the regulation of both the initiation and maintenance of tumorigenesis |
| 24589226 | Sensitization to TRAIL coincided with and depended on MYC upregulation and massive changes in gene regulation |
| 24589226 | Senescent cell-induced MYC silenced its target gene CFLAR, encoding the apoptosis inhibitor FLIPL , thus leading to the acquisition of TRAIL sensitivity |
| 24589226 | Altogether, our results reveal that senescent cell-secreted factors exert a TRAIL-sensitizing effect on pretransformed cells by modulating the expression of MYC and CFLAR |
| 24272483 | Mechanistically, depletion or pharmacologic inhibition of CypB caused hyperactivation of the oncogenic RAS-mitogen-activated protein kinase pathway, induction of cellular senescence signals, and death resulting from loss of MYC, mutant p53, Chk1, and Janus-activated kinase/STAT3 signaling |
| 24006061 | Studies in primary and tumor cells suggest that MYC plays an important role in regulating cellular senescence, thereby impacting on tumor development |
| 24006061 | Measurement of senescence is an important aspect of studies of MYC biology and will improve our understanding of MYC function and regulation both in preclinical and clinical settings |
| 24006061 | Measurement of senescence is an important aspect of studies of MYC biology and will improve our understanding of MYC function and regulation both in preclinical and clinical settings |
| 24006061 | This may form the basis for new concepts of pro-senescence therapy to combat MYC in cancer |
| 23804320 | Nuclear translocation enhanced FOXM1 transcriptional activity and promoted its downstream target gene c-Myc expression that could inhibit p21 expression |
| 23792448 | Treatment of PEL cell lines with BET inhibitors suppressed the expression of MYC and resulted in a genome-wide perturbation of MYC-dependent genes |
| 23792448 | Silencing of BRD4 and MYC expression blocked cell proliferation and cell-cycle progression, while ectopic expression of MYC from a retroviral promoter rescued cells from (+)-JQ1-induced growth arrest |
| 23792448 | Silencing of BRD4 and MYC expression blocked cell proliferation and cell-cycle progression, while ectopic expression of MYC from a retroviral promoter rescued cells from (+)-JQ1-induced growth arrest |
| 23792448 | Taken collectively, our results demonstrate that the utility of BET inhibitors may not be limited to cancers in which genomic alterations result in extremely high expression of MYC and they may have equal or perhaps greater activity against cancers in which the MYC genomic locus is structurally intact and c-Myc protein is deregulated at the post-translational level and is only modestly overexpressed |
| 23792448 | Taken collectively, our results demonstrate that the utility of BET inhibitors may not be limited to cancers in which genomic alterations result in extremely high expression of MYC and they may have equal or perhaps greater activity against cancers in which the MYC genomic locus is structurally intact and c-Myc protein is deregulated at the post-translational level and is only modestly overexpressed |
| 23503666 | Compared to the controls, telomerase activity, the expression of human telomerase reverse transcriptase (hTERT) and c-Myc in the irradiated HUVECs were downregulated during serial passage |
| 23321669 | KDM2B repressed developmental genes through cobinding with Polycomb group (PcG) proteins at transcriptional start sites, whereas it activated a module of metabolic genes, including mediators of protein synthesis and mitochondrial function, cobound by the MYC oncogene and the histone demethylase KDM5A |
| 23318426 | Here we demonstrate that the introduction of defined reprogramming factors (OCT4, SOX2, Klf4 and c-Myc) into MCF-10A nontumorigenic mammary epithelial cells, followed by partial differentiation, transforms the bulk of cells into tumorigenic CD44(+)/CD24(low) cells with CSC properties, termed here as induced CSC-like-10A or iCSCL-10A cells |
| 23242809 | UNLABELLED: MYC deregulation is common in human cancer |
| 23242809 | Deregulated expression of MYC results in increased mTOR complex 1 (mTORC1) signaling |
| 23242809 | Therefore, mTORC1-dependent evasion of senescence is critical for cellular transformation and tumor maintenance by MYC in B lymphocytes |
| 22836754 | B-Raf activation cooperates with PTEN loss to drive c-Myc expression in advanced prostate cancer |
| 22836754 | Accordingly, therapeutic treatments with rapamycin and PD0325901 to target these pathways, respectively, attenuate c-Myc levels and reduce tumor and metastatic burden |
| 22683798 | Two hiPSC lines, hiPSC (1) and hiPSC (2) were generated from human dermal fibroblasts using OCT-4, SOX-2, KLF-4, c-Myc via retroviral-based reprogramming |
| 22359668 | Prevention of LPA receptor engagement also promoted ubiquitination-mediated c-Myc elimination in MSCs, and consequently the entry into a quiescent state, G(0) phase, of the cell cycle |
| 22301954 | Conditional silencing of WRN expression in c-MYC overexpressing non-small cell lung cancer xenografts impaired both tumor establishment and tumor growth |
| 22197555 | Next, we found that SIRT1 increased hTERT transcription in a c-MYC-dependent manner, triggered the transcription of the c-MYC gene and increased the amount of c-MYC recruited to the hTERT promoter |
| 22197555 | Further, SIRT1 increased the transcriptional activation ability of c-MYC and correspondingly increased the amount of acetylated H4 histone at the hTERT promoter |
| 22197555 | All of these results indicated that SIRT1 activates hTERT transcription through the involvement of c-MYC, and suggested that this SIRT1-induced augmentation of hTERT transcription resulted in the extension of the cellular life span of HUC-F2 cells |
| 22190494 | The c-MYC oncoprotein, the NAMPT enzyme, the SIRT1-inhibitor DBC1, and the SIRT1 deacetylase form a positive feedback loop |
| 22190494 | Here we determined whether SIRT1 is downstream of the prototypic c-MYC oncogene, which is activated in the majority of tumors |
| 22190494 | Elevated expression of c-MYC in human colorectal cancer correlated with increased SIRT1 protein levels |
| 22190494 | Activation of a conditional c-MYC allele induced increased levels of SIRT1 protein, NAD(+), and nicotinamide-phosphoribosyltransferase (NAMPT) mRNA in several cell types |
| 22190494 | This increase in SIRT1 required the induction of the NAMPT gene by c-MYC |
| 22190494 | In primary human fibroblasts previously immortalized by introduction of c-MYC, down-regulation of SIRT1 induced senescence and apoptosis |
| 22190494 | Furthermore, SIRT1 directly bound to and deacetylated c-MYC |
| 22190494 | Enforced SIRT1 expression increased and depletion/inhibition of SIRT1 reduced c-MYC stability |
| 22190494 | Depletion/inhibition of SIRT1 correlated with reduced lysine 63-linked polyubiquitination of c-Myc, which presumably destabilizes c-MYC by supporting degradative lysine 48-linked polyubiquitination |
| 22190494 | Moreover, SIRT1 enhanced the transcriptional activity of c-MYC |
| 22190494 | Taken together, these results show that c-MYC activates SIRT1, which in turn promotes c-MYC function |
| 22190494 | Furthermore, SIRT1 suppressed cellular senescence in cells with deregulated c-MYC expression and also inhibited c-MYC-induced apoptosis |
| 22190494 | Constitutive activation of this positive feedback loop may contribute to the development and maintenance of tumors in the context of deregulated c-MYC |
| 22146591 | BAG2 is a target of the c-Myc gene and is involved in cellular senescence via the p21(CIP1) pathway |
| 22146591 | Suppression of c-Myc is likely to induce cellular senescence in many tumors with unclear mechanisms |
| 22146591 | A proteomics survey indicated that high levels of BCL2-associated athanogene 2 (BAG2) were found in response to c-Myc repression in TRE293 cells |
| 22011035 | Analysis of secretome changes uncovers an autocrine/paracrine component in the modulation of cell proliferation and motility by c-Myc |
| 22011035 | Because c-Myc overexpression is among the most frequent alterations in cancer, here we investigated the effect of sustained c-Myc expression on the secretome of a nontransformed human epithelial cell line (hT-RPE) |
| 22011035 | By using a quantitative proteomic approach, we have identified 125 proteins in conditioned media of hT-RPE/MycER cells upon c-Myc induction |
| 22011035 | Analysis of the 49 proteins significantly down-regulated by c-Myc revealed a marked enrichment of factors associated with growth inhibition and cellular senescence |
| 22011035 | Accordingly, media conditioned by hT-RPE cells expressing c-Myc show an increased ability to sustain hT-RPE cellular proliferation/viability |
| 22011035 | In accordance with these data, the expression of the majority of the genes encoding proteins down-regulated in hT-RPE was significantly reduced also in colorectal adenomatous polyps, early tumors in which c-Myc is invariably overexpressed |
| 22011035 | These findings help to elucidate the significance of c-Myc overexpression at early stages of tumor development and uncover a remarkable autocrine/paracrine component in the ability of c-Myc to stimulate proliferation, sustain tumor maintenance, and modulate cell migration |
| 21969595 | Lymphomas that recur after MYC suppression continue to exhibit oncogene addiction |
| 21969595 | The suppression of oncogenic levels of MYC is sufficient to induce sustained tumor regression associated with proliferative arrest, differentiation, cellular senescence, and/or apoptosis, a phenomenon known as oncogene addiction |
| 21969595 | However, after prolonged inactivation of MYC in a conditional transgenic mouse model of Emu-tTA/tetO-MYC T-cell acute lymphoblastic leukemia, some of the tumors recur, recapitulating what is frequently observed in human tumors in response to targeted therapies |
| 21969595 | Many of the recurring lymphomas (76%) harbored mutations in the tetracycline transactivator, resulting in expression of the MYC transgene even in the presence of doxycycline |
| 21969595 | Importantly, shRNA-mediated suppression of the high levels of MYC in recurring tumors elicited both suppression of proliferation and increased apoptosis, confirming that these tumors remain oncogene addicted |
| 21969595 | These results suggest that tumors induced by MYC remain addicted to overexpression of this oncogene |
| 25961265 | Furthermore, NaBu down-regulates the proto-oncogenes c-Myc, Cyclin D1 and E2F1 mRNA levels |
| 21921675 | Paradoxically, one of the cellular proliferative factors, c-Myc proto-oncogene also controls the expression of these CDKIs and modulates the fate of cell in response to DNA damage |
| 21889194 | BET bromodomain inhibition as a therapeutic strategy to target c-Myc |
| 21889194 | MYC contributes to the pathogenesis of a majority of human cancers, yet strategies to modulate the function of the c-Myc oncoprotein do not exist |
| 21889194 | Toward this objective, we have targeted MYC transcription by interfering with chromatin-dependent signal transduction to RNA polymerase, specifically by inhibiting the acetyl-lysine recognition domains (bromodomains) of putative coactivator proteins implicated in transcriptional initiation and elongation |
| 21889194 | Using a selective small-molecule bromodomain inhibitor, JQ1, we identify BET bromodomain proteins as regulatory factors for c-Myc |
| 21889194 | BET inhibition by JQ1 downregulates MYC transcription, followed by genome-wide downregulation of Myc-dependent target genes |
| 21889194 | Efficacy of JQ1 in three murine models of multiple myeloma establishes the therapeutic rationale for BET bromodomain inhibition in this disease and other malignancies characterized by pathologic activation of c-Myc |
| 21702981 | Suppression of CK2alpha by small-interfering RNA or the CK2alpha activity inhibitor emodin inhibited proliferation of CRC cells, caused G0/G1 phase arrest, induced cell senescence, elevated the expression of p53/p21 and decreased the expression of C-myc |
| 21678465 | Effects of a glycogen synthase kinase-3beta inhibitor (LiCl) on c-myc protein in intervertebral disc cells |
| 21678465 | In the present study, we provide evidence that the expression of c-myc, a key protein required for cell proliferation, is regulated by Wnt signaling |
| 21678465 | Our data also show that activation of Wnt signaling by LiCl, a Wnt signaling activator, leads to the suppression of c-myc promoter activity and expression |
| 21678465 | To ascertain whether Wnt signaling regulates the expression of c-myc, we measured both its transcript and protein expression |
| 21678465 | Following treatment with LiCl, c-myc expression was suppressed at both the mRNA and protein levels |
| 21678465 | In nucleus pulposus cells treated with c-myc, cell viability increased significantly, whereas treatment with a c-myc inhibitor decreased cell viability |
| 21678465 | Taken together, these results suggest that c-myc is an important factor that promotes the proliferation of nucleus pulposus cells |
| 21627565 | Chromatin immunoprecipitation was performed to investigate hTERT and cellular-myelocytomatosis (c-myc) promoters' activity |
| 21627565 | HER2 was found to mediate hTERT expression through activation of Nuclear Factor-kappa B (NF-kappaB) and c-myc |
| 21627565 | CONCLUSIONS: The present study suggests that following irradiation, HER2 receptor activates hTERT/telomerase, increasing the breast cancer cells' survival potential, through sequential induction of transcription factors NF-kappaBeta and c-myc |
| 21193900 | Our experiments demonstrated a declined left ventricular performance and decreased alteration in mitochondrial gene expression with age following T-H and we have identified c-Myc, a pleotropic transcription factor, to be the most upregulated gene in 6- and 22-month-old rats after T-H |
| 21193900 | The expression of c-Myc and cardiac death promoting gene Bnip3 were increased, and Pgc1-alpha and Ppar-alpha a decreased following T-H |
| 21120446 | Of note, HDAC7 deficiency was further identified to induce cellular senescence program, which was also reversed by c-Myc re-expression |
| 21120446 | Further chromatin immunoprecipitation assays indicated that HDAC7 directly binds with c-Myc gene and HDAC7 silencing decreased c-Myc mRNA level via reducing histone H3/H4 acetylation and repressing the association of RNA polymerase II (RNAP II) with c-Myc gene |
| 21120446 | Taken together, our findings highlight for the first time an unrecognized link between HDAC7 and c-Myc and offer a novel mechanistic insight into the contribution of HDAC7 to tumor progression |
| 21047732 | Paradoxically, G(1)-S phase genes such as MYC, CDK4, CDK6, CCND1, and CCND2 were strongly downregulated, in line with the observed G(1) arrest |
| 21037952 | MYC Inactivation Elicits Oncogene Addiction through Both Tumor Cell-Intrinsic and Host-Dependent Mechanisms |
| 21037952 | One of the most common oncogenic events in human cancer is the activation of the MYC oncogene |
| 21037952 | The inactivation of MYC may be a general and effective therapy for human cancer |
| 21037952 | Indeed, it has been experimentally shown that the inactivation of MYC can result in dramatic and sustained tumor regression in lymphoma, leukemia, osteosarcoma, hepatocellular carcinoma, squamous carcinoma, and pancreatic carcinoma through a multitude of mechanisms, including proliferative arrest, terminal differentiation, cellular senescence, induction of apoptosis, and the shutdown of angiogenesis |
| 21037952 | Hence, targeting the inactivation of MYC appears to elicit oncogene addiction and, thereby, tumor regression through both tumor cell-intrinsic and host-dependent mechanisms |
| 21035406 | Here, we show that an intact immune system, specifically CD4(+) T cells, is required for the induction of cellular senescence, shutdown of angiogenesis, and chemokine expression resulting in sustained tumor regression upon inactivation of the MYC or BCR-ABL oncogenes in mouse models of T cell acute lymphoblastic lymphoma and pro-B cell leukemia, respectively |
| 20969773 | Moreover, a slight upregulation of the oncogene c-Myc, along with an undetectable level of breast tumor-related gene Bag-1 and TRPS-1, was observed in BME65Cs cells while these genes are all highly expressed in MCF-7 |
| 20713526 | Intrinsic tumor-suppressor pathways protect healthy cells from transformation by activated oncogenes like MYC or RAS through induction of apoptosis or cellular senescence, respectively |
| 20713526 | However, when expressed together, MYC and RAS evade these barriers and initiate tumorigenesis |
| 20445224 | Proto-oncogenes such as MYC and RAS promote normal cell growth but fuel tumor development when deregulated |
| 20445224 | When expressed together MYC and RAS are sufficient for oncogenic transformation of primary rodent cells, but the basis for their cooperativity has remained unresolved |
| 20382143 | Deregulation of MYC as a consequence of carciogenic events enforces cells to undergo a transition to a hyperproliferative state |
| 20053783 | Disabling c-Myc in childhood medulloblastoma and atypical teratoid/rhabdoid tumor cells by the potent G-quadruplex interactive agent S2T1-6OTD |
| 20053783 | S2T1-6OTD proved to be a potent c-Myc inhibitor through its high-affinity physical interaction with the G-quadruplex structure in the c-Myc promoter |
| 20053783 | Treatment with S2T1-6OTD reduced the mRNA and protein expressions of c-Myc and hTERT, which is transcriptionally regulated by c-Myc, and decreased the activities of both genes |
| 20053783 | Under conditions where inhibition of both proliferation and c-Myc activity was observed, S2T1-6OTD treatment decreased the protein expression of the cell cycle activator cyclin-dependent kinase 2 and induced cell cycle arrest |
| 20052289 | In contrast, knockdown of IFI16 expression in cells increased the expression of c-Myc, a positive regulator of hTERT expression |
| 20052289 | Additionally, over-expression of IFI16 protein in cells inhibited the c-Myc-mediated stimulation of the activity of hTERT-luc-reporter and reduced the steady-state levels of c-Myc and hTERT |
| 20010815 | Cdk2 suppresses cellular senescence induced by the c-myc oncogene |
| 19966300 | The MYC and RAS oncogenes are frequently activated in cancer and, together, are sufficient to transform rodent cells |
| 19696787 | During senescence, miR-34a targets the important proto-oncogene MYC and our data suggest that miR-34a thereby coordinately controls a set of cell cycle regulators |
| 19433493 | PTTG1 activates c-Myc in NIH 3T3 cells, suggesting a role in cell transformation |
| 19235838 | FoxM1 depletion led to the down-regulation of its target genes c-MYC and Skp2, coupled with the accumulation of the CDK inhibitor p27(kip1) |
| 19054066 | Platination of telomeric sequences and nuclease hypersensitive elements of human c-myc and PDGF-A promoters and their ability to form G-quadruplexes |
| 19054066 | The telomeric regions of DNA and nuclease hypersensitive elements of human c-myc and PDGF-A promoters represent a very appealing target for cisplatin and may interfere with normal DNA function |
| 18668528 | Recently, isolation of patient-specific induced pluripotent stem (iPS) cells was achieved by transducing fibroblasts with four transcription factors, Oct4, Sox2, Klf4, and c-Myc |
| 18158869 | METHODS: BMMS-03 cells and hMSC from the bone marrow of a 4-month-old elicited fetus, were transiently transfected with the pcDNA3-hbxip plasmid encoding the HBXIP gene and pSilencer-hbxip plasmid encoding RNA interference (RNAi) targeting HBXIP mRNA, followed by the examination of the hTERT promoter reporter gene by luciferase assay, and the detection of telomerase activity by telomeric repeat amplication protocol, respectively, as well as the expression levels of hTERT, c-Myc, and Bcl-2 by Western blot analysis |
| 18158869 | RESULTS: The overexpression of HBXIP led to a significant upregulation of hTERT promoter activity, telomerase activity, and the expression levels of hTERT, c-Myc, and Bcl-2 in BMMS-03 cells |
| 18084761 | The expression levels of telomerase catalytic subunit hTERT and oncogenic MYC in essential thrombocythemia are affected by the molecular subtype |
| 18084761 | One direct transcriptional activator of hTERT is the oncogene MYC which is known to be, in turn, activated by JAK2 |
| 18084761 | To explore the relationship of telomerase, MYC and JAK2 in chronic myeloproliferative diseases, we investigated hTERT and MYC expression in bone marrow cells of essential thrombocythemia (ET) and polycythemia vera (PV) |
| 18084761 | To explore the relationship of telomerase, MYC and JAK2 in chronic myeloproliferative diseases, we investigated hTERT and MYC expression in bone marrow cells of essential thrombocythemia (ET) and polycythemia vera (PV) |
| 18084761 | We could determine an up-regulation of MYC expression exclusively in JAK2(wt) ET, whereas hTERT expression was rather inconsistent across the groups |
| 18084761 | Interestingly, a significant correlation between MYC and hTERT expression could only be established in homozygous JAK2(V617F) PV and control cases |
| 18084761 | Thus, the functional link between MYC and hTERT seems to be impaired depending on the molecular ET subtype, which in turn may have implications on the phenotype and course of the disease |
| 17986575 | Several Ets transcription factors are involved in regulating hTERT gene expression, both directly and indirectly through the proto-oncogene c-myc |
| 17664422 | Cellular senescence is an important mechanism of tumor regression upon c-Myc inactivation |
| 17664422 | Here we report that the suppression of the c-Myc (MYC) oncogene induces cellular senescence in diverse tumor types including lymphoma, osteosarcoma, and hepatocellular carcinoma |
| 17664422 | Here we report that the suppression of the c-Myc (MYC) oncogene induces cellular senescence in diverse tumor types including lymphoma, osteosarcoma, and hepatocellular carcinoma |
| 17664422 | MYC inactivation was associated with prototypical markers of senescence, including acidic beta-gal staining, induction of p16INK4a, and p15INK4b expression |
| 17664422 | Moreover, MYC inactivation induced global changes in chromatin structure associated with the marked reduction of histone H4 acetylation and increased histone H3 K9 methylation |
| 17664422 | Osteosarcomas engineered to be deficient in p16INK4a or Rb exhibited impaired senescence and failed to exhibit sustained tumor regression upon MYC inactivation |
| 17664422 | Similarly, only after lymphomas were repaired for p53 expression did MYC inactivation induce robust senescence and sustained tumor regression |
| 17664422 | The pharmacologic inhibition of signaling pathways implicated in oncogene-induced senescence including ATM/ATR and MAPK did not prevent senescence associated with MYC inactivation |
| 17664422 | Our results suggest that cellular senescence programs remain latently functional, even in established tumors, and can become reactivated, serving as a critical mechanism of oncogene addiction associated with MYC inactivation |
| 17569615 | These inhibitory effects of IFI16 were associated with upregulation of p21 and inhibition of cyclin E, cyclin D1, c-Myc and Ras |
| 17473528 | The mRNA expressions of Smad3 increased, but those of c-myc and nucleostemin decreased with the length hMSCs were in in vitro culture |
| 17151361 | Mel-18, a polycomb group protein, regulates cell proliferation and senescence via transcriptional repression of Bmi-1 and c-Myc oncoproteins |
| 17151361 | Importantly, using promoter-reporter, chromatin immunoprecipitation, and quantitative real-time primary transcript RT-PCR assays, and an RNA interference approach, we demonstrate that Bmi-1 is a bona fide target of c-Myc oncoprotein |
| 17151361 | Finally, our data suggest that Mel-18 regulates Bmi-1 expression during senescence via down-regulation of c-Myc |
| 17151361 | These studies link c-Myc and polycomb function in cell proliferation and senescence |
| 17102614 | Cellular senescence, epigenetic switches and c-Myc |
| 17102614 | We recently found that human fibroblasts or endothelial cells with genetically-engineered reduction of proto-oncogene c-Myc expression switched with an increased frequency to a senescent state by a telomere-independent mechanism involving the polycomb group repressor Bmi-1 and the cyclin-dependent kinase inhibitor p16(INK4a) |
| 17100566 | The results may have two important implications for oncogene-blocking therapies: (i) downregulation of oncogenes, for instance HER2, MYC, RAS, RAF, BCR-ABL or WNT1, usually leads to a rapid tumor remission |
| 16818632 | MYC can induce DNA breaks in vivo and in vitro independent of reactive oxygen species |
| 16818632 | MYC overexpression is thought to initiate tumorigenesis by inducing cellular proliferation and growth and to be restrained from causing tumorigenesis by inducing cell cycle arrest, cellular senescence, and/or apoptosis |
| 16818632 | Here we show that MYC can induce DNA breaks both in vitro and in vivo independent of increased production of reactive oxygen species (ROS) |
| 16818632 | We provide an insight into the specific circumstances under which MYC generates ROS in vitro and propose a possible mechanism |
| 16818632 | We found that MYC induces DNA double-strand breaks (DSBs) independent of ROS production in murine lymphocytes in vivo as well as in normal human foreskin fibroblasts (NHFs) in vitro in normal (10%) serum, as measured by gammaH2AX staining |
| 16818632 | In NHFs cultured in low versus normal serum, MYC induced increased expression of CYP2C9, a gene product well known to be associated with ROS production |
| 16818632 | Hence, MYC overexpression can induce ROS and SSBs under some conditions, but generally induces widespread DSBs in vivo and in vitro independent of ROS production |
| 16537449 | Reduced c-Myc signaling triggers telomere-independent senescence by regulating Bmi-1 and p16(INK4a) |
| 16537449 | Normal human fibroblasts with one copy of the c-myc gene inactivated by targeted homologous recombination switched with an increased frequency to a telomere-independent senescent state mediated by the cyclin-dependent kinase inhibitor p16(INK4a) |
| 16537449 | The Myc-Bmi circuit provides a mechanism for the conversion of environmental inputs that converge on c-Myc into discrete cell-fate decisions coupled to cell-cycle recruitment |
| 16319532 | Drug-induced changes in the expression of c-myc and p21(WAF1), and in their respective protein levels, were observed |
| 16167342 | This loss results in persistent expression of hMad4, which leads to an inability to switch from an hMad4/Max complex to a c-Myc/Max complex on selected c-Myc target genes following serum stimulation |
| 16167342 | In reporter assays, Miz-1 enhances reporter GFP expression; this enhancement is inhibited by co-expressing c-Myc |
| 16167342 | Thus hMad4, as does its murine counterpart, contains the Inr element through which Miz-1 activates its expression; but this action is inhibited in the presence of c-Myc |
| 16167342 | This inhibition may explain the down-regulation of hMad4, corresponding to the up-regulation of c-Myc, in young serum-starved quiescent fibroblasts upon serum stimulation |
| 16167342 | However, this reciprocal change does not occur in replicatively senescent fibroblasts upon serum stimulation; instead, hMad4 persists in the presence of high levels of c-Myc activation |
| 16167342 | Our results suggest that: (1) replicative senescence-specific factors may block c-Myc inhibition of Miz-1 activation of hMad4 expression; and (2) the continual presence of hMad4 protein may transcriptionally repress selected c-Myc target genes, whose functions are key to the signaling pathways leading to apoptosis inhibition and permanent exit of cell cycle traverse in normal human fibroblasts |
| 16055741 | Overexpression of hPNPase(OLD-35) in human melanoma cells and melanocytes induces distinctive changes associated with senescence, potentially mediated by direct degradation of c-myc mRNA by this enzyme |
| 16055741 | Moreover, either one of the two RPH domains induced the morphological, biochemical, and gene expression changes associated with senescence, including degradation of c-myc mRNA |
| 16055741 | The present study elucidates how a predominantly mitochondrial protein, via its localization in both mitochondria and cytoplasm, is able to target a specific cytoplasmic mRNA, c-myc, for degradation and through this process induce cellular senescence |
| 15098029 | The translation factor eIF-4E promotes tumor formation and cooperates with c-Myc in lymphomagenesis |
| 15098029 | We found that c-Myc overrides eIF-4E-induced cellular senescence, whereas eIF-4E antagonizes c-Myc-dependent apoptosis in vivo |
| 14563552 | Induction of endogenous telomerase (hTERT) by c-Myc in WI-38 fibroblasts transformed with specific genetic elements |
| 14563552 | Transduced cells exhibited anchorage independence in soft agar and expressed increased levels of c-Myc and endogenous hTERT |
| 14563552 | These findings indicate that the widely used model system of WI-38 fibroblasts can be employed for transformation studies using defined genetic elements and that the endogenous hTERT and c-Myc are induced in these cells during early tumorigenesis |
| 14563552 | Such studies should have important implications in the mechanisms of hTERT and c-Myc induction in the beginning stages of tumorigenesis and facilitate extension of these studies to novel models of tumorigenesis in cellular senescence |
| 12842909 | The MYC oncoprotein is a transcription factor that coordinates cell growth and division |
| 12842909 | MYC overexpression exacerbates genomic instability and sensitizes cells to apoptotic stimuli |
| 12842909 | Here we demonstrate that MYC directly stimulates transcription of the human Werner syndrome gene, WRN, which encodes a conserved RecQ helicase |
| 12842909 | The overexpression of MYC in WRN syndrome fibroblasts or after WRN depletion from control fibroblasts led to rapid cellular senescence that could not be suppressed by hTERT expression |
| 12842909 | We propose that WRN up-regulation by MYC may promote MYC-driven tumorigenesis by preventing cellular senescence |
| 11846374 | Microarray gene screening reveals that quiescent and senescent cells, in comparison with replicating ones, are characterized by downregulation of Pam, a protein associated with c-Myc, and upregulation of Mad family genes, Max dimerization proteins |
| 11846374 | Moreover, quiescence and senescence can be distinguished by increased expression of Irlb, c-Myc transcription factor, and Miz-1, c-Myc-interacting Zn finger protein 1, only in the former state |
| 11795494 | Immortalization of human embryonic fibroblasts by overexpression of c-myc and simian virus 40 large T antigen |
| 11795494 | We attempted to find out what this alteration is by overexpressing cellular signal mediator genes; c-myc and cyclin D frequently amplified in many cancer cells |
| 11795494 | Overexpression of cyclin D did not affect the immortalization, but, overexpression of c-myc along with T antigen could immortalize normal human diploid fibroblast |
| 11795494 | Several cellular markers tested during immortalization process showed that p21, a cyclin-dependent kinase inhibitor and a marker of cellular senescence, disappeared in the life span-extended cells by T antigen and in the immortalized cells by c-myc |
| 11795494 | These results suggest that overexpression of c-myc contributes to immortalization of human diploid fibroblast by activating telomerase activity and suppressing p21 activity |
| 11283613 | Alleles of c-myc that are unable to bind to Miz-1 fail to inhibit accumulation of p15INK4b messenger RNA in primary cells and are, as a consequence, deficient in immortalization |
| 10963125 | The mechanisms regulating hTERT expression have been extensively analyzed, and transcriptional regulation of hTERT has been found to be essential for hTERT expression, in which several nuclear factors including c-Myc play crucial roles |
| 10648922 | One oncogene that might activate TERT in the natural context is c-myc |
| 10606235 | We also found that estrogen activates c-Myc expression in MCF-7 cells and that E-boxes in the hTERT promoter that bind c-Myc/Max play additional roles in estrogen-induced transactivation of hTERT |
| 10593857 | Several proto-oncogenes and tumor suppressor genes have been implicated in the regulation of telomerase activity, both directly and indirectly; these include c-Myc, Bcl-2, p21(WAF1), Rb, p53, PKC, Akt/PKB, and protein phosphatase 2A |
| 10561724 | Finally, migrated or unmigrated cells were examined for the expression of c-fos and c-myc by in situhybridization |
| 9642304 | Induction of c-fos/c-myc expression by epidermal growth factor decreases with alteration of their gene binding proteins in senescent fibroblasts |
| 9642304 | OBJECTIVE: To observe the changes of proto-oncogene c-fos/c-myc expression and its relation to specific transcription factors in human senescent fibroblast after epidermal growth factor (EGF) addition |
| 9642304 | METHODS: The c-fos/c-myc expression were analysed by Northern blot |
| 9642304 | RESULTS: (1) The expression of c-fos/c-myc was less susceptible to induction by EGF as the cells aged |
| 9642304 | CONCLUSIONS: Inability of c-fos/c-myc gene induction by EGF in senescent cells might be correlated with some DNA-binding proteins |
| 9521854 | Accelerated proliferative senescence of rat embryo fibroblasts after stable transfection of multiple copies of the c-Myc DNA-binding sequence |
| 9521854 | The protooncogene c-myc positively regulates cellular proliferation whereas it exhibits negative effects on both cellular senescence and differentiation |
| 9521854 | Ectopic overexpression of c-myc in transfection experiments or titration of the c-myc mRNA by antisense oligonucleotides has demonstrated that small changes of the concentration of cellular c-myc mRNA or protein levels can be crucial for these processes |
| 9521854 | In view of the role of c-Myc as a transcription factor, most of these effects may be mediated via its binding to specific DNA sequences |
| 9521854 | Here we studied the cellular reactions after manipulating the cellular concentration of c-Myc DNA-binding sites |
| 9521854 | Multiple copies of the c-Myc-binding sequence GACCACGTGGTC or, alternatively, the control sequence GACCAGCTGGTC that displays only a poor affinity for c-Myc were stably introduced into the genome of rat embryo fibroblasts |
| 8853900 | However, serum-stimulated myotubes display a typical immediate-early response, including the up-regulation of c-fos, c-jun, c-myc, and ld-1 |
| 7776985 | Changes of the methylation pattern of the c-myc gene during in vitro aging of IMR90 human embryonic fibroblasts |
| 7776985 | As the expression of c-myc affects strongly cellular aging and terminal differentiation, we have analysed the sequence-specific methylation pattern of the c-myc gene during proliferative aging in vitro of human embryonic fibroblasts |
| 7616677 | Senescent cells showed the strong transcriptional repressions of early serum responsive genes (c-fos, c-jun, c-myc), late responsive genes of transcription factor E2F1 and cyclin E |
| 8294468 | In senescent cells, serum barely induced the Id-1H and Id-2H mRNAs, although the levels of c-myc expression induced were similar in early passage and senescent cells |
| 1537881 | Treatment of HOME cells with EGF significantly increased cellular mRNA levels of tissue-type plasminogen activator, and two protooncogenes, c-fos and c-myc, in young HOME cells, but not in senescent HOME cells |
| 2104680 | Irreversible changes in gene expression occurred in senescent human fetal lung fibroblasts: a non-cell cycle-regulated mRNA was partially repressed; an unusual polyadenylated histone mRNA was expressed; although serum induced c-H-ras, c-myc, and ornithine decarboxylase mRNA normally, ornithine decarboxylase activity was deficient; and serum did not induce mRNA for a replication-dependent histone and for the c-fos proto-oncogene |
| 3403538 | The time course and the magnitude of the expression of c-myc, an early G1 gene, were quite similar in young and senescent IMR-90 cells and appeared to be PDL-independent |
| 3283652 | Transcription of the c-myc oncogene is altered in spontaneously immortalized rodent fibroblasts |
| 3283652 | We have analysed the role of the cellular oncogene, c-myc in the process of in vitro cellular ageing and spontaneous cellular immortalization using rodent fibroblasts |
| 3283652 | The steady-state level of c-myc of mouse and rat fibroblasts does not change significantly during cellular ageing in vitro |
| 3283652 | By contrast, the steady state level of c-myc mRNA increases 3- to 20-fold upon spontaneous establishment of these rodent fibroblasts |
| 3283652 | The changes in the steady-state level of c-myc mRNA are not due to gene amplification nor to gross gene rearrangements or translocations |
| 3283652 | However, the response of the myc gene to growth factor stimulation is present apparently equally in both mortal and immortal cells; a difference is seen in an increased maintenance of high c-myc mRNA levels after growth stimulation in established cell lines |
| 3283652 | Both young and senescent mortal cells, as well as immortal cells, respond to mitogen stimulation with a sharp increase in c-myc mRNA levels |
| 3283652 | We also demonstrated that the c-myc mRNA levels do not respond to serum concentration above a minimum level, nor do they respond to factors in the conditioned medium of immortal cell cultures |
| 3494524 | Additionally, the EGF-induced expression of specific competence genes (c-myc, JE, KC) is decreased, whereas the induction of c-fos gene expression by EGF is unaltered by TGF-beta treatment |
| 2434812 | When senescent human diploid cells, TIG-1, were stimulated with serum at the end of their proliferative life span, such biochemical events as uptakes of 2-deoxyglucose and uridine, and expression of c-myc, were enhanced |
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