MicroRNA-184 inhibits cell proliferation and invasion, and specifically targets TNFAIP2 in Glioma

Abstract

Background: miRNA-184 is an oncogene in human hepatocellular carcinoma but acts as a tumor suppressor in tongue squamous cell carcinoma. Studies have shown that miR-184 was down-regulated in glioma and TNFα-induced protein 2 (TNFAIP2) was closely related to tumorigenesis. This study aimed to determine the functions of miR-184 in glioma and the mechanisms of miRNA-184-TNFAIP2 mediated glioma progression. Methods: Real-time reverse-transcription PCR detected expression of miR-184 and TNFAIP2. U87 and U251 cells were transfected with miR-184 mimic, inhibitor, or negative control miRNA, and their invasion abilities were assayed. Cellular proliferation was measured by the cell counting kit-8 assay. miR-184 effects on glioma cell apoptosis and cell cycle were assessed by flow cytometer. Biological information software have predicted that miR-184 could target TNFα-induced protein 2 (TNFAIP2), Which was further validated by Western blot and qRT-PCR in glioma cells. In vivo, U87 cells transduced with either lentiviral over-expressed miR-184 or control lentivirus were injected into nude mice subcutaneously and intracranial respectively. Results: Expression of miR-184 was significantly lower in glioma tissues and cell-lines compared to normal brain tissues. Protein and mRNA expression of TNFAIP2 were inversely correlated with miR-184 in glioma. In vitro, proliferation and invasion abilities were also decreased in U87 and U251 cells after transfection with miR-184 mimic. In vivo, the xenografted tumor size in the miR-184 overexpressing group were smaller than the miR-NC group. Concordantly, U87 and U251 cells transfected with miR-184 mimic had a higher apoptosis rate, triggering an accumulation of cells at the G0/G1 phase and decreased cells in S-phase. Conclusions: miR-184 could regulate TNFAIP2 expression and affected its translation in glioma. miR-184 could also inhibit glioma progression and might serve as a novel therapeutic target in glioma.