title: Loss of brain-enriched miR-124 microRNA enhances stem-like traits and invasiveness of glioma cells.
abstract: miR-124 is a brain-enriched microRNA that plays a crucial role in neural development and has been shown to be down-regulated in glioma and medulloblastoma, suggesting its possible involvement in brain tumor progression. Here, we show that miR-124 is down-regulated in a panel of different grades of glioma tissues and in all of the human glioma cell lines we examined. By integrated bioinformatics analysis and experimental confirmation, we identified SNAI2, which is often up-regulated in glioma, as a direct functional target of miR-124. Because SNAI2 has been shown to regulate stem cell functions, we examined the roles of miR-124 and SNAI2 in glioma cell stem-like traits. The results showed that overexpression of miR-124 and knockdown of SNAI2 reduced neurosphere formation, CD133(+) cell subpopulation, and stem cell marker (BMI1, Nanog, and Nestin) expression, and these effects could be rescued by re-expression of SNAI2. Furthermore, enhanced miR-124 expression significantly inhibited glioma cell invasion in vitro. Finally, stable overexpression of miR-124 and knockdown of SNAI2 inhibited the tumorigenicity and invasion of glioma cells in vivo. These findings reveal, for the first time, that the tumor suppressor activity of miR-124 could be partly due to its inhibitory effects on glioma stem-like traits and invasiveness through SNAI2.
authors.affiliation: Brain Tumour Centre and Division of Neurosurgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong,; Department of Chemistry, The University of Hong Kong, Hong Kong,; Department of Surgery, Yijishan Hospital of Wannan Medical College, Sun Yat-Sen University, Guangzhou.
authors.forename: Hongping
authors.initials: H
authors.lastname: Xia
authors.affiliation: Department of Chemistry, The University of Hong Kong, Hong Kong.
authors.forename: William K C
authors.initials: WKC
authors.lastname: Cheung
authors.affiliation: Department of Chemistry, The University of Hong Kong, Hong Kong.
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Ng
authors.affiliation: Department of Surgery, Yijishan Hospital of Wannan Medical College, Sun Yat-Sen University, Guangzhou.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-Sen University, Guangzhou.
authors.forename: Songshan
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Brain Tumour Centre and Division of Neurosurgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong,; Department of Chemistry, The University of Hong Kong, Hong Kong.
authors.forename: Johnny
authors.initials: J
authors.lastname: Sze
authors.affiliation: Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
authors.forename: Gilberto K K
authors.initials: GKK
authors.lastname: Leung
authors.affiliation: Brain Tumour Centre and Division of Neurosurgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong.
authors.forename: Gang
authors.initials: G
authors.lastname: Lu
authors.affiliation: Brain Tumour Centre and Division of Neurosurgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong.
authors.forename: Danny T M
authors.initials: DTM
authors.lastname: Chan
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Chongqing, China, and.
authors.forename: Xiu-Wu
authors.initials: XW
authors.lastname: Bian
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Chongqing, China, and; Stanley Ho Centre for Emerging Infectious Diseases and State Key Laboratory in Oncology in South China and the School of Biomedical Sciences, Faculty of Medicine and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Hsiang-Fu
authors.initials: HF
authors.lastname: Kung
authors.affiliation: Brain Tumour Centre and Division of Neurosurgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong,. Electronic address: wpoon@cuhk.edu.hk.
authors.forename: Wai Sang
authors.initials: WS
authors.lastname: Poon
authors.affiliation: Brain Tumour Centre and Division of Neurosurgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong,; Department of Chemistry, The University of Hong Kong, Hong Kong,; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Chongqing, China, and. Electronic address: mcllin@surgery.cuhk.edu.hk.
authors.forename: Marie C
authors.initials: MC
authors.lastname: Lin
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001932:Brain Neoplasms; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D000071250:Snail Family Transcription Factors; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D000943:Antigens, Differentiation; D014408:Biomarkers, Tumor; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; C000604408:SNAI2 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors