miR-216b-5p  Promotes the Migration and Invasion of LN-229 Glioma Cells by Targeting BTN3A2

Accumulating evidence indicated that microRNAs (miRNA) play an important role in tumor invasion and metastasis by regulating their target genes.However, whether the miRNA-216b-5p(miR-216b-5p ) and their target genes butyrophilin subfamily 3 member A2(BTN3A2) promote glioma invasion and metastasis is unclear.This study aims to study whether miR-216b-5p  promoted migration and invasion in glioma cells by negatively regulating BTN3A2.The differential expression analysis of GSE15824 and GSE4290 was analyzed by GEO2R.We found that only BTN3A2 is up-regulated in both GSE15824 and GSE4290 (P<0.05).The gene set enrichment analysis (GSEA) analysis indicated BTN3A2 was related to many cancer-related pathways (P<0.05).The results of survival curves showed that the overall survival of patients with high expression of BTN3A2 decreased significantly (P <0.001).The expression of BTN3A2 was increased with the increase of WHO grade (P<0.05), while the expression of BTN3A2 was increased in 1p/19q uncombined deletion and IDH mutant patients (P<0.001).Western blotting results showed that BTN3A2 was up-regulated in seven glioma tissues and glioma cell lines U87, U251 and LN-229 and downregulated in the miR-216b-5p  mimics group; Transwell results showed that transfection with BTN3A2 silencing plasmids(si-BTN3A2) or miR-216b-5p  mimics plasmids could inhibit the ability of migration and invasion in LN-229 cells in vitro (P<0.05).The online websites predicted miR-216b-5p  as a potential target gene of BTN3A2.The survival curve results show that compared with patients with low expression of miR-216b-5p , the survival rate of patients with high expression was significantly increased (P=0.025).The relative expression of miR-216b-5p  was decreased in U87, U251 and LN229 cells was detected by real time quantitative PCR (P<0.05).The results of dual luciferase assay showed that BTN3A2 could bind to miR-216b-5p (P<0.05).Transwell experiment results showed that overexpression of miR-216b-5p  can inhibit the migration and invasion ability of LN229 cells (P<0.05).In summary, miR-216b-5p  promotes the migration and invasion by targeting BTN3A2 of LN-229 glioma cells.