The transcription factor nuclear factor kappa B (NF-kappaB) and the long non-coding RNA (lncRNA) HOTAIR (HOX transcript antisense RNA) have diverse functional roles in cancer
In this study, we show that upregulation of HOTAIR induced platinum resistance in ovarian cancer, and increased HOTAIR levels were observed in recurrent platinum-resistant ovarian tumors vs primary ovarian tumors
To investigate the role of HOTAIR during DNA damage induced by platinum, we monitored double-strand breaks and show that HOTAIR expression results in sustained activation of DNA damage response (DDR) after platinum treatment
We demonstrate that ectopic expression of HOTAIR induces NF-kappaB activation during DDR and interleukin-6 and interleukin-6 expression, both key NF-kappaB target genes
We show that HOTAIR regulates activation of NF-kappaB by decreasing Ikappa-Balpha (NF-kappaB inhibitor) and establish that by inducing prolonged NF-kappaB activation and expression of NF-kappaB target genes during DNA damage, HOTAIR has a critical role in cellular senescence and platinum sensitivity
HOTAIR associates with E3 ubiquitin ligases bearing RNA-binding domains, Dzip3 and Mex3b, as well as with their respective ubiquitination substrates, Ataxin-1 and Snurportin-1
In this manner, HOTAIR facilitates the ubiquitination of Ataxin-1 by Dzip3 and Snurportin-1 by Mex3b in cells and in vitro, and accelerates their degradation
