title: MiR-330-mediated regulation of SH3GL2 expression enhances malignant behaviors of glioblastoma stem cells by activating ERK and PI3K/AKT signaling pathways.
abstract: MicroRNAs are currently considered as an active and rapidly evolving area for the treatment of tumors. In this study, we elucidated the biological significance of miR-330 in glioblastoma stem cells (GSCs) as well as the possible molecular mechanisms. SH3GL2 is mainly distributed in the central nervous system and considered to be a tumor suppressor in many tumors. In the present study, we identified miR-330 as a potential regulator of SH3GL2 and we found that it was to be inversely correlated with SH3GL2 expression in GSCs which were isolated from U87 cell lines. The expression of miR-330 enhanced cellular proliferation, promoted cell migration and invasion, and dampened cell apoptosis. When the GSCs were co-transfected with the plasmid containing short hairpin RNA directed against human SH3GL2 gene and miR-330 mimic, we found that miR-330 promoted the malignant behavior of GSCs by down-regulating the expression of SH3GL2. Meanwhile, the ERK and PI3K/AKT signaling pathways were significantly activated, leading to the decreased expression of apoptotic protein and increased expression of anti-apoptotic protein. Furthermore, in orthotopic mouse xenografts, the mice given stable over-expressed SH3GL2 cells co-transfected with miR-330 knockdown plasmid had the smallest tumor sizes and longest survival. In conclusion, these results suggested that miR-330 negatively regulated the expression of SH3GL2 in GSCs, which promoted the oncogenic progression of GSCs through activating ERK and PI3K/AKT signaling pathways. The elucidation of these mechanisms will provide potential therapeutic approaches for human glioblastoma.
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People's Republic of China.
authors.forename: Yilong
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning Province, People's Republic of China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang, Liaoning Province, People's Republic of China.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning Province, People's Republic of China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang, Liaoning Province, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning Province, People's Republic of China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang, Liaoning Province, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Shang
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning Province, People's Republic of China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang, Liaoning Province, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning Province, People's Republic of China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang, Liaoning Province, People's Republic of China.
authors.forename: Libo
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Neurology, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning Province, People's Republic of China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People's Republic of China.
authors.forename: Shengtao
authors.initials: S
authors.lastname: Qu
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning Province, People's Republic of China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People's Republic of China.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Liu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C570805:MIRN330 microRNA, human; D035683:MicroRNAs; C107640:SH3GL2 protein, human; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
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