title: MiR-152 functions as a tumor suppressor in glioblastoma stem cells by targeting Krüppel-like factor 4.
abstract: Glioblastoma (GBM) is the most common central nervous system tumor and the molecular mechanism driving its development is still largely unknown, limiting the treatment of this disease. In the present study, we explored the potential role of miR-152 in glioblastoma stem cells (GSCs) as well as the possible molecular mechanisms. Our results proved that miR-152 was down-regulated in human GSCs. Restoring the expression of miR-152 dramatically reduced the cell proliferation, cell migration and invasion as well as inducing apoptosis. Mechanistic investigations defined Krüppel-like factor 4 (KLF4) as a direct and functional downstream target of miR-152, which was involved in the miR-152-mediated tumor-suppressive effects in GSCs. Meanwhile, this process was coincided with the down-regulated LGALS3 that could be bound and promoted by KLF4, leading to attenuate the activation of MEK1/2 and PI3K signal pathways. Moreover, the in vivo study showed that miR-152 over-expression and KLF4 knockdown produced the smallest tumor volume and the longest survival in nude mice. Taken together, these results elucidated the function of miR-152 in GSCs progression and suggested a promising application of it in glioma treatment.
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Yilong
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, China.
authors.forename: Lini
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, China. Electronic address: xueyixue888@163.com.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Xue
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D001798:Blood Proteins; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D037502:Galectin 3 / Q000378:metabolism; D037161:Galectins; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D048370:MAP Kinase Kinase 2 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D014407:Tumor Cells, Cultured
chemical_list: D020413:3' Untranslated Regions; D001798:Blood Proteins; D037502:Galectin 3; D037161:Galectins; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C428445:LGALS3 protein, human; C550856:MIRN152 microRNA, human; D035683:MicroRNAs; C482128:MAP2K2 protein, human; D058539:Phosphatidylinositol 3-Kinase; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482125:MAP2K1 protein, human
keywords: Glioblastoma; KLF4; MiR-152; MicroRNAs; Stem cells