MicroRNA-125a-5p targets LIM kinase 1 to inhibit cisplatin resistance of cervical cancer cells.

ABSTRACT: Cervical cancer (CC), also known as invasive cervical carcinoma, is one of the most common gynecologic malignancies. The aim of the present study was to investigate the function of microRNA (miR)-125a-5p on CC progression and cisplatin (DDP) resistance. For this purpose, reverse transcription-quantitative PCR (RT-qPCR) was used to assess the expression of miR-125a-5p and LIMK1 in CC tissues, corresponding normal tissues and cells (human CC cell lines: C-33A, CaSKi; human cervical epithelial cells: HUCEC). Cisplatin (DDP) resistant cervical cancer cell lines were established (C-33A/DDP and CaSKi/DDP cell lines). RT-qPCR results demonstrated that miR-125a-5p or LIM kinase 1 (LIMK1) expression was downregulated or upregulated in C-33A/DDP and CaSKi/DDP cells, respectively. MTT assay, flow cytometry analysis and Western blotting were employed to detect the proliferation, apoptosis rate, IC₅₀ of DDP and the expression of drug resistance-related proteins (P-glycoprotein and glutathione S-transferase-π). The targeting relationship between miR-125a-5p and LIMK1 was confirmed by the TargetScan database and dual-luciferase reporter gene assay. In CC tissues and cell lines, compared with normal tissues or HUCEC, miR-125a-5p expression was downregulated and LIMK1 expression was upregulated. The transfection with miR-125a-5p mimics decreased the proliferation of CaSKi/DDP cells, increased the apoptosis rate, reduced the IC₅₀ of DDP, and downregulated the expression of drug resistance-related proteins; conversely, LIMK1 overexpression decreased the apoptosis rate, increased the IC₅₀ of DDP, and upregulated the expression of drug resistance-related proteins. The luciferase reporter gene assay demonstrated that miR-125a-5p targeted and negatively regulated LIMK1. miR-125a-5p could partially reverse the effect of LIMK1 on the proliferation, apoptosis, IC₅₀ of DDP and the expressions of drug resistance-related proteins. The findings of the present study indicated that miR-125a-5p sensitizes CC cells to DDP by targeting LIMK1, hence increasing the anticancer efficacy of cisplatin.

SUBMITTER: Xu Y 

PROVIDER: S-EPMC7988690 | biostudies-literature |

REPOSITORIES: biostudies-literature