MicroRNA-433-3p enhances chemosensitivity of glioma to cisplatin by downregulating NR5A2.

Abstract

We attempted to investigate influence of microRNA-433-3p on malignant progression of glioma and identify its molecular mechanism, thus laying groundwork for glioma management. Expression data along with clinical data of glioma were accessed from the TCGA database for differential and survival analyses to look for the target differentially expressed genes. Quantitative reverse transcriptase PCR (qRT-PCR) and western blot were utilized to assess NR5A2 mRNA and protein expression in different glioma cell lines, respectively. MTT, Transwell assay, and flow cytometry were carried out to assay the impact of NR5A2 on behaviors of glioma cells in vitro. Bioinformatics analysis was used to identify the upstream microRNA of NR5A2 in glioma, while dual-luciferase and western blot assays were used to detect binding of microRNA and NR5A2. Chemosensitivity of glioma cells was evaluated by cisplatin cytotoxicity test. NR5A2 was upregulated in both glioma tissues and cell lines. Dual-luciferase assay result showed binding site of microRNA-433-3p on NR5A2 mRNA 3'UTR, and microRNA-433-3p reduced NR5A2 expression. Cell assays revealed that silencing NR5A2 could hamper proliferation, invasion, and migration and enhance chemosensitivity to cisplatin while promoting glioma cell apoptosis and blocking glioma cells in G0/G1 phase. Rescue experiments also indicated that microRNA-433-3p suppressed glioma malignant progression via inhibiting NR5A2. MicroRNA-433-3p which is significantly poorly expressed in glioma targets NR5A2 to suppress glioma malignant progression and enhance chemosensitivity to cisplatin.