MiR-325-3p inhibits chemotherapy resistance of the ovarian cancer cell line SKOV3 by targeting HE4

WANG Heng

doi:10.3969/j.issn.1002-7386.2024.20.002

Abstract：Objective To investigate the effect of miR-325-3p on cisplatin(CDDP)resistance of the ovarian cancer cell line SKOV3 by targeting human epididymis protein 4(HE4).Methods The CDDP-resistant ovarian cancer cell line SKOV3/DDP was established by DDP induction with a gradient concentration.The cell counting kit-8(CCK-8)assay was performed to detect the CDDP resistance of SKOV3 cells and SKOV3/DDP cells treated with CDDP at varied concentrations.Subsequently,SKOV3/DDP cells were treated with blank control,or transfected with negative control and miR-325-3p mimic.The half maximal inhibitory concentration(IC50)was measured by CCK-8 assay.Cell apoptosis was examined by flow cytometry.The binding site between miR-325-3p and HE4 3'UTR was predicted in the TargetScan,and verified by dual-luciferase reporter assay.Quantitative real-time PCR(qRT-PCR)was used to detect the mRNA expression of miR-325-3p and HE4.Western blotting was performed to detect the protein expression of HE4.Results The IC50 of SKOV3 and SKOV3/DDP against CDDP was 14.15μmol/L,and 45.29μmol/L,respectively.The resistance index(RI)was 3.20.Compared with the parental cells,miR-325-3p was significantly downregulated in SKOV3/DDP cells,while the mRNA and protein levels of HE4 were significantly upregulated(all P＜0.05).There were no significant differences in miR-325-3p expression,mRNA and protein expressions of HE4,IC50 and cell apoptotic rate in cells treated with blank control versus those transfected with negative control(P＞0.05).Transfection of miR-322-3p mimic significantly upregulated miR-325-3p and increased apoptotic rate,and decreased IC50 and mRNA and protein levels of HE4(all P＜0.05).Conclusion MiR-325-3p inhibits CDDP resistance of ovarian cancer cells by targeting HE4.