MiR-29a Inhibits Glioma Tumorigenesis through a Negative Feedback Loop of TRAF4Akt Signaling

Abstract EN

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.