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微小 RNA-640 靶向 SLIT1 通过抑制 Wnt/β-连环蛋白信号通路的激活增强胶质瘤的放射敏感性。

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

机构信息

Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Department of Neurology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

出版信息

Br J Biomed Sci. 2022 Apr 7;79:10067. doi: 10.3389/bjbs.2022.10067. eCollection 2022.

Abstract

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. 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. 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. 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.

摘要

本研究旨在分析 miR-640-SLIT1 轴和 Wnt/β-catenin 信号通路对神经胶质瘤细胞放射敏感性的影响。采用 RT-qPCR 检测神经胶质瘤组织和神经胶质瘤细胞系 U251 和 A172 中 miR-640 和 SLIT 导向配体 1(SLIT1)的相对表达。用 si-SLIT1 或 miR-640 抑制剂转染细胞系,研究神经胶质瘤细胞的放射敏感性。采用 CCK-8 法检测细胞活性,划痕愈合试验检测细胞迁移,Transwell 试验检测细胞侵袭, caspase-3 法检测细胞凋亡。SLIT1 在神经胶质瘤组织和细胞系中上调,与放射敏感性呈负相关。其敲低降低了 U251 和 A17 细胞的放射抗性、迁移和侵袭,但增加了细胞凋亡。miR-640 活性丧失上调了 U251 和 A17 细胞中 SLIT1、Wnt 和 β-catenin 蛋白的表达,同时抑制了 p-GSK-3β 蛋白水平。这些结果表明,miR-640 通过 SLIT1 和 Wnt/β-catenin 信号通路介导神经胶质瘤细胞的放射敏感性。调节 Wnt/β-catenin 信号通路的 miR-640-SLIT1 轴可能是联合放疗有效治疗神经胶质瘤的一种治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e20f/9302537/f3660018e892/bjbs-79-10067-g001.jpg

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