NF-κB1, c-Rel, and ELK1 inhibit miR-134 expression leading to TAB1 upregulation in paclitaxel-resistant human ovarian cancer.

Abstract

The mechanism by which the transcription factors inhibit the miRNA expression in ovarian cancer chemoresistance is unclear. The present study investigated the mechanism underlying the transcriptional repression of miR-134 in chemoresistant serous epithelial ovarian cancer. The results demonstrate that NF-κB1, c-Rel, and ELK1 are involved as transcription factors in repressing miR-134 expression in paclitaxel-resistant ovarian cancer cells. Knockdown of these transcription factors led to increased miR-134 expression, resulting in increased apoptosis and inhibition of proliferation in SKOV3-TR30 cells. NF-κB1, c-Rel, and ELK1 mRNA expression was upregulated in chemoresistant specimens and negatively correlated with miR-134 expression. Kaplan–Meier analysis revealed that high nuclear expressions of NF-κB1, c-Rel, ELK1 were significantly associated with short survival in serous epithelial ovarian cancer patients. Finally, TAB1 was identified as a functional target of miR-134, and the expression of TAB1 was increased by the transcription factors of NF-κB1, c-Rel, and ELK1 via miR-134. Taken together, these results provide an insight into the mechanism of repressed miR-134 expression in chemoresistance of serous epithelial ovarian cancer.