MicroRNA-10b mediates TGF-β1-regulated glioblastoma proliferation, migration and epithelial-mesenchymal transition

Ma,Chengyuan; Wei,Feng; Xia,Huan; Liu,Haiyu; Dong,Xuechao; Zhang,Yandong; Luo,Qinghua; Liu,Yan; Li,Yang

doi:10.3892/ijo.2017.3947

MicroRNA-10b mediates TGF-β1-regulated glioblastoma proliferation, migration and epithelial-mesenchymal transition

Authors:
- Chengyuan Ma
- Feng Wei
- Huan Xia
- Haiyu Liu
- Xuechao Dong
- Yandong Zhang
- Qinghua Luo
- Yan Liu
- Yang Li
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Affiliations: Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Hepatobiliary and Pancreas Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Intensive Care Unit, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Rheumatology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Genetic Engineering Laboratory of PLA, The Eleventh Institute of Academy of Military Medical Sciences of PLA, Changchun, Jilin 130122, P.R. China
Published online on: April 4, 2017 https://doi.org/10.3892/ijo.2017.3947
Pages: 1739-1748

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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.

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