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NF-κB-HOTAIR axis links DNA damage response, chemoresistance and cellular senescence in ovarian cancer.


ABSTRACT: The transcription factor nuclear factor kappa B (NF-κB) 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-κB activation during DDR and interleukin-6 and interleukin-6 expression, both key NF-κB target genes. We show that HOTAIR regula

SUBMITTER: Ozes AR 

PROVIDER: S-EPMC5050052 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature