miR-548b inhibits the proliferation and invasion of malignant gliomas by targeting metastasis tumor-associated protein-2.

Abstract

microRNAs (miRNAs) play important roles in cancer development and progression. In this study, we explored the expression and biological roles of miR-548b in human gliomas. The expression of miR-548b in human glioma tissues and cell lines was examined. Gain-of-function experiments were conducted to determine the roles of miR-548b in glioma cell growth, invasiveness, and tumorigenesis. Bioinformatic analysis and luciferase reporter assays were performed to identify direct target genes for miR-548b. miR-548b was underexpressed in human glioma tissues and cell lines. Re-expression of miR-548b significantly inhibited the proliferation and colony formation of U87 and U373 glioma cells. Enforced expression of miR-548b significantly impaired the invasiveness of glioma cells. Notably, metastasis tumor-associated protein-2 (MTA2) was a direct target of miR-548b. Overexpression of miR-548b negatively regulated endogenous MTA2 expression in U87 cells. Rescue experiments with an MTA2 construct lacking the 3'-untranslated region showed that enforced expression of MTA2 significantly restored cell proliferation and invasion in miR-548b-overexpressing cells. In-vivo studies confirmed that miR-548b overexpression retarded the growth of U87 xenograft tumors, which was accompanied by reduced expression of MTA2. In conclusion, miR-548b exerts its tumor-suppressive activity in glioma through repression of MTA2. Restoration of miR-548b may have therapeutic potential in glioma.

• Authors: Yunzhi Pan, Wenna Liang, Xiaoyang Zhao, Luping Liu, Yang Qing, Yongmei Li
• Journal: Neuroreport (Neuroreport) Vol. 27 Issue 17 Pg. 1266-1273 (Dec 07 2016) ISSN: 1473-558X [Electronic] England
• PMID: 27682888 (Publication Type: Journal Article)

Chemical References

• 3' Untranslated Regions
• MIRN548 microRNA, human
• MicroRNAs
• MAT2A protein, human
• Methionine Adenosyltransferase

Topics

• 3' Untranslated Regions (genetics)
• Animals
• Brain Neoplasms (genetics, metabolism)
• Carcinogenicity Tests
• Cell Cycle (physiology)
• Cell Line, Tumor
• Cell Proliferation (physiology)
• Colony-Forming Units Assay
• Computational Biology
• Gene Expression Regulation, Neoplastic (physiology)
• Glioma (genetics, metabolism)
• HEK293 Cells
• Humans
• Methionine Adenosyltransferase (genetics, metabolism)
• Mice
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Neoplasm Invasiveness (genetics, physiopathology)
• Statistics, Nonparametric
• Transfection