MicoRNA-214-3p: a key player in CPLX2-mediated inhibition on temozolomide resistance in glioma

Abstract

ABSTRACT Objective This study plans to investigate whether miR-214-3p could bind CPLX2 to regulate temozolomide (TMZ) resistance in glioma. Methods The differential expression of miR-214-3p and CPLX2 was determined by qRT-PCR and Western blotting in TMZ-resistant glioma tissues. Then, TMZ-resistant glioma cells (U87/TMZ and U251/TMZ) were established and transfected with miR-214-3p mimic, miR-214-3p inhibitor, pcDNA3.1-CPLX2 or pcDNA3.1-CPLX2 plus miR-214-3p mimic to evaluate the impact of miR-214-3p and CPLX2 on the proliferation, apoptosis and TMZ resistance in U87/TMZ and U251/TMZ cells. The binding relationship between miR-214-3p and CPLX2 was reported by dual-luciferase reporter assay. Results Higher miR-214-3p and lower CPLX2 expression levels were revealed in TMZ-sensitive glioma tissues. The alterations in miR-214-3p and CPLX2 expression were more significant in TMZ-resistant tissues compared with TMZ-sensitive tissues. In cellular experiments, TMZ-resistant cells expressed higher miR-214-3p expression and lower CPLX2 expression than TMZ-sensitive cells. Transfection of miR-214-3p mimic elevated the proliferation and half maximal inhibitory concentration (IC50) and decreased the apoptosis in U87/TMZ and U251/TMZ cells. Introduction of miR-214-3p inhibitor or pcDNA3.1-CPLX2 reduced the proliferation and IC50 value and prompted the apoptosis in TMZ-resistant glioma cells. The effects of pcDNA3.1-CPLX2 on inhibiting the proliferation and IC50 value and enhancing the apoptosis in TMZ-resistant glioma cells were hindered by the transfection of miR-214-3p mimic. In addition, CPLX2 was a target gene of miR-214-3p. Conclusion Downregulation of miR-214-3p inhibits TMZ resistance in glioma by promoting CPLX2.