MicroRNA-218 inhibits glioma invasion, migration, proliferation, and cancer stem-like cell self-renewal by targeting the polycomb group gene Bmi1.
Malignant gliomas are the most common central nervous system tumors and the molecular mechanism driving their development and recurrence is still largely unknown, limiting the treatment of this disease. Here, we show that restoring the expression of miR-218, a microRNA commonly downregulated in glioma, dramatically reduces the migration, invasion, and proliferation of glioma cells. Quantitative reverse transcription PCR and Western blotting analysis revealed that expression of the stem cell-promoting oncogene Bmi1 was decreased after overexpression of miR-218 in glioma cells. Mechanistic investigations defined Bmi1 as a functional downstream target of miR-218 through which miR-218 ablated cell migration and proliferation. We documented that miR-218 also blocked the self-renewal of glioma stem-like cells, consistent with the suggested role of Bmi1 in stem cell growth. Finally, we showed that miR-218 regulated a broad range of genes involved in glioma cell development, including Wnt pathways that suppress glioma cell stem-like qualities. Taken together, our findings reveal miR-218 as a tumor suppressor that prevents migration, invasion, proliferation, and stem-like qualities in glioma cells.
Authors' Affiliations: Departments of Experimental Surgery, Neurosurgery, and Administration, Tangdu Hospital, Fourth Military Medical University; Department of Cell Biology, School of Basic Medical Sciences, Xi'an Medical University, Xi'an; Department of Bio-Nano-Science and Engineering, Institute of Micro-Nano Science and Technology; and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
Yanyang
Y
Tu
Xingchun
X
Gao
Gang
G
Li
Hualin
H
Fu
Daxiang
D
Cui
Hui
H
Liu
Weilin
W
Jin
Yongsheng
Y
Zhang
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D048054:Mitogen-Activated Protein Kinase 7 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014945:Wound Healing
D014408:Biomarkers, Tumor; C547471:MIRN218 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D008156:Luciferases; C481581:MAPK7 protein, human; D048054:Mitogen-Activated Protein Kinase 7