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

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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… Click to show full abstract

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.

Keywords: glioma tumorigenesis; expression; traf4 akt; mir 29a

Journal Title: BioMed Research International
Year Published: 2018

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