title: MicroRNA-10b mediates TGF-β1-regulated glioblastoma proliferation, migration and epithelial-mesenchymal transition.
abstract: Although it is well known that exaggerated proliferation, metastasis and the mesenchymal subtype is related with worst prognoses in glioblastoma (GBM) and that transforming growth factor-β1 (TGF-β1) is a potent factor in regulating the proliferation, migration and epithelial-mesenchymal transition (EMT) phenotype of GBM, the detailed mechanisms are still far from elucidated. MicroRNAs (miRNAs) are small non-coding RNAs which play critical roles in various diseases by regulating target gene expression. We report that miR-10b, a molecule downstream of TGF-β1, is involved in TGF-β1-regulated GBM cell proliferation, migration and EMT. We found that exposure of GBM cells to TGF-β1 significantly upregulated miR-10b expression. Overexpression of miR-10b promotes GBM cell proliferation, migration and EMT, whereas depletion of miR-10b obtained reverse effects. Further studies uncovered that some tumor-associated genes including epithelial cadherin (E-cadherin), apoptotic protease activating factor 1 (Apaf-1) and phosphatase and tensin homolog (PTEN) are target genes of miR-10b. In human GBM xenografts, antagomiR directed against miR-10b markedly suppressed tumor growth, and the tumor volume shrunk from 1252.5±285 to 873.4±205 mm3 after antagomiR‑10b treatment for 3 weeks compared with the control group (P<0.01). Taken together, our data collectively demonstrate that the proliferation, migration and EMT features of GBM cells can be regulated by TGF-β1 stimulation through controlling miR-10b. Thus, our findings provide a rationale for targeting TGF-β1 or miR-10b for the treatment of GBM.
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Chengyuan
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wei
authors.affiliation: Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Huan
authors.initials: H
authors.lastname: Xia
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Haiyu
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Intensive Care Unit, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Xuechao
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Rheumatology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yandong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Genetic Engineering Laboratory of PLA, The Eleventh Institute of Academy of Military Medical Sciences of PLA, Changchun, Jilin 130122, P.R. China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Genetic Engineering Laboratory of PLA, The Eleventh Institute of Academy of Military Medical Sciences of PLA, Changchun, Jilin 130122, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D000070416:Antagomirs / Q000008:administration & dosage / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D000070416:Antagomirs; C547183:MIRN10 microRNA, human; D035683:MicroRNAs; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1