MicroRNA-125a-5p targets LIM kinase 1 to inhibit cisplatin resistance of cervical cancer cells
Yongqian Xu, Yujie Zheng, Yan Duan, Lin Ma, Ping Nan
Journal:Oncology Letters
IF:2.97
DOI:10.3892/ol.2021.12653
PMID:33777215
Published:2021-03-18
research field:肿瘤学神经科学细胞生物学
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, IC<sub>50</sub> 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 IC<sub>50</sub> of DDP, and downregulated the expression of drug resistance‑related proteins; conversely, LIMK1 overexpression decreased the apoptosis rate, increased the IC<sub>50</sub> 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, IC<sub>50</sub> of DDP and the expressions of drug resistance‑related proteins. The findings of the
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