MiR-491 functions as a tumor suppressor through Wnt3a/β-catenin signaling in the development of glioma

Y. Meng, F.-R. Shang, Y.-L. Zhu

Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China. bxpu75@163.com

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• Oncology

OBJECTIVE: Glioma is the most frequent brain tumor that has high invasion and usually disperses to the whole brain through blood and basement membranes. MicroRNA-491 (miR-491) has been reported to have low expression and act as a tumor suppressor in several cancers. The Wnt/β-catenin signaling is a classic signaling pathway that participated in several biological processes. Our purpose was to detect the molecular mechanism of miR-491 in regulating the growth and metastasis of glioma.

MATERIALS AND METHODS: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was applied to calculate the mRNA level of miR-491 and target gene. The protein expression of special genes was assessed by Western blot. The proliferation and invasive abilities were measured by the Cell Counting Kit-8 (CCK-8) and transwell assays. The Kaplan-Meier method was conducted to evaluate the association between the expressions of miR-491 with the overall survival of glioma patients.

RESULTS: We discovered that miR-491 was lowly expressed in glioma and downregulation of miR-491 predicted poor outcome of glioma patients. Similarly, a high expression of miR-491 suppressed the growth and metastasis in glioma cell line LN229. MiR-491 high expression inhibited the growth of glioma in a mouse xenograft model. Moreover, Wnt3a was a target gene of miR-491 and miR-491 mediated the invasion-mediated epithelial-mesenchymal transition (EMT) by regulating the expression of Wnt3a. Additionally, miR-491 regulated the proliferation through the Wnt/β-Catenin pathway by targeting Wnt3a.

CONCLUSIONS: MiR-491 overexpression inhibited the proliferation through the Wnt3a/β-catenin pathway and invasion-mediated EMT in glioma. The newly identified miR-491/Wnt3a/β-catenin axis provides novel insight into the pathogenesis of glioma.

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