MicroRNA-101 inhibits proliferation, migration and invasion of human glioblastoma by targeting SOX9
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Nan Liu1,*, Lei Zhang1,6,*, Zhen Wang1, Yingduan Cheng1,2, Pengxing Zhang1, Xin Wang3, Weihong Wen4, Hongwei Yang3, Hui Liu1, Weilin Jin5, Yongsheng Zhang1, Yanyang Tu1,3
1Department of Experimental Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, China
2Department of Research Office, Cipher Ground, North Brunswick, NJ 08902, USA
3Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
4Department of Immunology, Fourth Military Medical University, Xi’an 710032, China
5Institute of Nano Biomedicine and Engineering, Department of Instrument Science and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of Ministry of Education, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
6Department of Orthopedics, Xi’an Children’s Hospital, Xi’an 710003, China
*These authors have contributed equally to this work
Weilin Jin, email: [email protected]
Yongsheng Zhang, email: [email protected]
Yanyang Tu, email: [email protected]
Keywords: MiR-101, SOX9, invasion, migration, proliferation
Received: June 29, 2016 Accepted: November 22, 2016 Published: November 30, 2016
Glioblastoma multiforme (GBM) is the most common primary malignant tumors originating in the brain parenchyma. At present, GBM patients have a poor prognosis despite the continuous progress in therapeutic technologies including surgery, radiotherapy, photodynamic therapy, and chemotherapy. Recent studies revealed that miR-101 was remarkably down-regulated in kinds of human cancers and was associated with aggressive tumor cell proliferation and stem cell self-renewal. Data also showed that miR-101 was down-regulated in primary glioma samples and cell lines, but the underlying molecular mechanism of the deregulation of miR-101 in glioma remained largely unknown. In this study, we found that miR-101 could inhibit the proliferation and invasion of glioma cells both in vitro and in vivo by directly targeting SOX9 [sex-determining region Y (SRY)-box9 protein]. Silencing of SOX9 exerted similar effects with miR-101 overexpression on glioma cells proliferation and invasion. Quantitative reverse transcription PCR and Western blotting analysis revealed a negative relationship between miR-101 and SOX9 in human glioma U251MG and U87MG cells, and the luciferase assay indicated that miR-101 altered SOX9 expression by directly targeting on 3’UTR. Taken together, our findings suggest that miR-101 regulates glioma proliferation, migration and invasion via directly down-regulating SOX9 both in vitro and in vivo, and miR-101 may be a potential therapeutic target for future glioma treatment.
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