MiR-30a-5p/CHD1 axis enhances cisplatin sensitivity of ovarian cancer cells via inactivating the Wnt/β-catenin pathway.

Abstract

Oovarian cancer is a common lethal gynecological malignancy with a high occurrence and dismal prognosis on account of its drug resistance. MicroRNAs (miRNAs) are widely involved in the chemotherapy resistance of tumors, including miR-30a-5p. Herein, we probed the functional role and molecular mechanism of miR-30a-5p in the chemoresistance of ovarian cancer. We enrolled 48 ovarian cancer patients in this study. Statistical analysis and a series of experiments including quantitative reverse transcription polymerase chain reaction, western blot, methyl thiazolyl tetrazolium assay, colony formation assay, flow cytometry analysis, Transwell assay, luciferase reporter assay, RNA pull-down assay and TOP/FOP flash assay were explored in the study. Animal experiments were performed to verify the role of miR-30a-5p in vivo . In our study, miR-30a-5p showed a prominently low level in ovarian cancer tissues and cells. Importantly, its expression in cisplatin-resistant cell lines was more downregulated than in cisplatin-sensitive ones. Additionally, miR-30a-5p overexpression inhibited proliferative, migratory and invasive abilities of ovarian cancer cells while enhancing cell apoptosis and improving cell sensitivity to cisplatin in ovarian cancer. Further, miR-30a-5p targeted to chromodomain helicase DNA binding protein 1 (CHD1) and inhibited the expression of CHD1 in ovarian cancer. Moreover, rescue experiments manifested that miR-30a-5p weakened cisplatin resistance and the cellular process of ovarian cancer by mediating CHD1. Besides, miR-30a-5p regulated CHD1 expression to suppress Wnt/β-catenin signaling in ovarian cancer. The findings were verified by in vivo experiments. This article elucidated that miR-30a-5p/CHD1 axis inhibited the cellular process and enhanced cisplatin sensitivity of ovarian cancer cells through the Wnt/β-catenin pathway, which may provide a useful direction for the targeted chemotherapy of ovarian cancer.