MiR-34c/SOX9 axis regulates the chemoresistance of ovarian cancer cell to cisplatin-based chemotherapy

Cisplatin (DDP)-based chemotherapy is a standard strategy for ovarian cancer (OC), while chemoresistance remains a major therapeutic challenge. Transcription factor SOX9 has been reported to be associated with tumor cell proliferation, metastasis, and chemoresistance. In the current study, we observed a higher SOX9 expression in OC cell lines; SOX9 overexpression might aggravate the chemoresistance of the OC cell to DDP, whereas its knockdown enhanced the chemoresistance. We screened for candidate microRNAs (miRNAs) which might target SOX9 using online tools and further verified the effect of miR-34c, one of the candidate miRNA that significantly inhibited SOX9 expression, in the regulation of OC cell proliferation and chemoresistance to DDP. Further, we verified the interaction between SOX9 and miR-34c, as well as the involvement of beta-catenin signaling in this process. Through the analysis of the correlation between miR-34c expression and the clinical features of patients with OC, we revealed that miR-34c might inhibit OC cell proliferation and chemoresistance to improve the prognosis of patients with OC. Further, the expression of SOX9, beta-catenin, and c-Myc in OC tissues was upregulated and inversely correlated with miR-34c expression, indicating that rescuing miR-34c expression, thus to inhibit SOX9, beta-catenin, and c-Myc expression presents a promising strategy of reducing the chemoresistance of the OC cell to DDP.