MiR-29a Inhibits Glioma Tumorigenesis through a Negative Feedback Loop of TRAF4/Akt Signaling

BACKGROUND: MiR-29a is known as a repressor of human cancer. However, its relevance in glioma proliferation and invasion remains largely unknown. In this study, we aimed to investigate the function and mechanism of miR-29a in glioma tumorigenesis. METHODS: The expression of miR-29a was determined by using qRT-PCR. CCK-8, wound healing, and transwell invasion assays were carried out to analyze the effects of miR-29a in glioblastoma cells. qRT-PCR, luciferase reporter, and western blot experiments were done to validate the targeting of TRAF4/Akt pathway by miR-29a. The expression correlation between levels of TRAF4 and miR-29a was analyzed. Regulation of miR-29a expression by enhanced/reduced TRAF4/Akt expression was finally confirmed by qRT-PCR. RESULTS: MiR-29a was decreased in the glioma tissues, especially in those at higher grades. Following its mimic transfection, we validated that miR-29a inhibited cell proliferation, migration, and invasion. Consistently, miR-29a inhibition induced the opposite effects on cell proliferation, migration, and invasion. We confirmed TRAF4 as a direct target of miR-29a, which might mediate the Akt pathway activation. We showed a significantly negative expression correlation between TRAF4 and miR-29a in normal and glioma tissues. Finally we observed an upregulation of miR-29a in TRAF4/Akt activated cells. CONCLUSION: MiR-29a is critical tumor suppressor for glioma tumorigenesis by forming a negative feedback loop of TRAF4/Akt signaling and represents a potent therapeutic candidate for treating gliomas.