title: MicroRNA-126 acts as a tumor suppressor in glioma cells by targeting insulin receptor substrate 1 (IRS-1).
abstract: MicroRNA (miR-126) was reported to be downregulated and to act as a tumor suppressor in cancers of the lung, cervix, bladder, breast, liver and prostate. However, the precise roles and underling mechanisms of miR-126 in glioma remain largely unknown. This study is aimed to study the role of miR-126 in the progression of glioma and to elucidate underlying miR-126-mediated mechanisms in glioma. Our results revealed that miR-126 was downregulated in the collected glioma specimen, compared with non-cancerous brain tissues. Restored miR-126 expression inhibited cell proliferation, colony formation, migration and invasion, and induced cell cycle arrest at G0/G1 phase and cell apoptosis of U-87 MG glioma cells. Overexpression of miR-126 was also able to suppress the growth of U-87 MG glioma xenografts in mice. Furthermore, insulin receptor substrate 1 (IRS-1) were identified as a target of miR-126, and showed that it was negatively regulated by miR-126 in glioma cells. We also demonstrated that overexpression of miR-126 suppressed PI3K and AKT activation, which contribute to suppress tumor growth of glioma. Taken together, these findings showed that miR-126 functions as a tumor suppressor in glioma cells by targeting IRS-1 expression via the PI3K/AKT signaling pathways, suggesting that miR-126 might be a novel target for therapeutic strategies in glioma.
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University Changchun 130021, Jilin Province, P. R. China.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Luan
authors.affiliation: Department of Ophthalmology, The Second Hospital of Jilin University Changchun 130041, Jilin Province, P. R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zuo
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University Changchun 130021, Jilin Province, P. R. China.
authors.forename: Shuyan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University Changchun 130021, Jilin Province, P. R. China.
authors.forename: Guangming
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University Changchun 130021, Jilin Province, P. R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Peng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: PI3K/AKT; glioma; insulin receptor substrate 1; miR-126