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

• Published in: Human cell : official journal of Human Cell Research Society 2019-10, Vol.32 (4), p.548-556
• Main Authors: Xu, Tong-Jiang, Qiu, Peng, Zhang, Yu-Bao, Yu, Sheng-Yuan, Xu, Guang-Ming, Yang, Wei
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Biomedical and Life Sciences; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Brain Neoplasms - therapy; Cell Biology; Cell differentiation; Cell growth; Cell migration; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Cell Survival - genetics; Cell viability; Gene Expression; Glioblastoma; Glioblastoma - genetics; Glioblastoma - pathology; Glioblastoma - therapy; Glioblastoma cells; Gynecology; Humans; Integrins - genetics; Integrins - metabolism; Integrins - physiology; Invasiveness; Life Sciences; Male; Mice, Nude; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; MicroRNAs - physiology; miRNA; Molecular Targeted Therapy; Neoplasm Invasiveness - genetics; Neoplasm Transplantation; Oncology; Phenotypes; Reporter gene; Reproductive Medicine; Research Article; Reverse transcription; RNA, Messenger - metabolism; Stem Cells; Surgery; Therapeutic applications; Tumor Cells, Cultured; Tumorigenicity; Tumors; Xenografts
• ISSN: 1749-0774; 0914-7470; 1749-0774
• DOI: 10.1007/s13577-019-00279-9

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.