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MiR-148a inhibits the proliferation and migration of glioblastoma by targeting ITGA9

胶质母细胞瘤 U87型 细胞生长 小RNA 癌症研究 免疫印迹 活力测定 细胞凋亡 干细胞 生物 基因 细胞生物学 生物化学 遗传学
作者
Tong-jiang Xu,Ping Qiu,Yubao Zhang,Shengyuan Yu,Guofeng Xu,Yang Wu
出处
期刊:Human Cell [Springer Science+Business Media]
卷期号:32 (4): 548-556 被引量:27
标识
DOI:10.1007/s13577-019-00279-9
摘要

Glioblastoma is a common malignant primary intracranial tumor characterized by rapid invasive growth and a high recurrence rate after surgery. MicroRNAs (miRNAs) are involved in cell proliferation, differentiation, and apoptosis, and abnormal miRNA expression is associated with the occurrence and progression of various tumors, including glioblastomas. The aim of this study was to determine the levels of miR-148a and integrin subunit alpha 9 (ITGA9) in glioblastoma tissues and cells and their involvement in cancer cell proliferation and migration. Glioblastoma tissues from 19 patients and two glioblastoma cell lines (U87 and LN229) were used in this study. The effects of miR-148a on cell viability, proliferation, colony formation, migration, and invasion were assessed. Glioblastomas were xenografted in nude mice to examine the effects of miR-148a overexpression on tumor growth in vivo. Levels of ITGA9 mRNA and protein in glioblastoma tissues were detected by quantitative reverse transcription PCR and western blot analysis, respectively. The interaction between miR-148a and ITGA9 was determined by a dual-luciferase reporter gene assay. We found that the overexpression of miR-148a decreases the proliferation, clustering, migration, and invasiveness of U87 and LN229 cells and inhibits the tumorigenicity of xenografted glioblastomas. We confirmed that ITGA9 is the target of miR-148a. Restoration of ITGA9 expression reversed the decreased viability, migration, and invasiveness of glioblastoma cells induced by miR-148a overexpression. Our findings indicate that miR-148a can suppress the malignant phenotype of glioblastoma by targeting ITGA9 and identify ITGA9 as a potential therapeutic target for glioblastoma.

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