Micro RNA-640 Targeting SLIT1 Enhances Glioma Radiosensitivity by Restraining the Activation of Wnt/β-Catenin Signaling Pathway.

Abstract

Purpose: The purpose of this study was to analyze the effects of miR-640-SLIT1 axis and the Wnt/β-catenin signaling pathway on radiosensitivity of glioma cells. Methods: Relative expressions of miR-640 and slit guidance ligand 1 (SLIT1) in glioma tissues and glioma cell lines U251 and A172 were detected using RT-qPCR. The cell lines were transfected with si-SLIT1 or miR-640 inhibitor to study the radiosensitivity of glioma cells. We detected cell activity using CCK-8 assay, cell migration using wound healing assay, cell invasion using transwell assay, and apoptosis using caspase-3 assay. Results: SLIT1 was upregulated in glioma tissues and cell lines, and inversely correlated with radiation sensitivity. Its knockdown reduced radioresistance, migration, and invasion, but increased apoptosis in U251 and A17 cells. Loss of miR-640 activity upregulated SLIT1, Wnt, and β-catenin protein expression, whereas it inhibited p-GSK-3β protein levels in U251 and A17 cells. These results suggest that miR-640 mediates the radiosensitivity of glioma cells through SLIT1 and the Wnt/β-catenin signaling pathway. Conclusion: The miR-640-SLIT1 axis that regulates the Wnt/β-catenin signaling pathway is a possible therapeutic option for the effective treatment of glioma in combination with radiotherapy.