miR-548b inhibits the proliferation and invasion of malignant gliomas by targeting metastasis tumor-associated protein-2.
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.
aDepartment of Neurology, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar bDepartment of Neurology, Liaocheng Third People's Hospital, Liaocheng Departments of cOrthopaedic Medicine dNuclear Medicine eRehabilitation Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, China.
Yunzhi
Y
Pan
Wenna
W
Liang
Xiaoyang
X
Zhao
Luping
L
Liu
Yang
Y
Qing
Yongmei
Y
Li
D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism*; D015197:Carcinogenicity Tests; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D003114:Colony-Forming Units Assay; D019295:Computational Biology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005910:Glioma / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008716:Methionine Adenosyltransferase / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000503:physiopathology; D018709:Statistics, Nonparametric; D014162:Transfection
D020413:3' Untranslated Regions; C561887:MIRN548 microRNA, human; D035683:MicroRNAs; C527161:MAT2A protein, human; D008716:Methionine Adenosyltransferase