期刊
EXPERIMENTAL AND MOLECULAR PATHOLOGY
卷 100, 期 1, 页码 160-166出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.yexmp.2015.12.010
关键词
OS; miRNA; miR-205; TGF-alpha; Cell proliferation; Invasion; Migration
类别
资金
- Taizhou Science and Technology Program [2012221055TZ]
Osteosarcoma (OS) is the most common primary bone cancer, and it is most prevalent in children and young adults. The prognosis of OS remains poor, and survival of OS reached a plateau. The discovery of microRNAs (miRNAs) provides a new possibility for the early diagnosis and treatment of OS. In this study, we detected the expression level of miR-205 and Transforming growth factor-alpha (TGF-alpha) in 15 cases of clinical OS tissues and adjacent normal bone tissues. We found that the expression of miR-205 was significantly lower in OS tissues than in normal bone tissues; the expression of TGF-alpha mRNA was significantly increased in OS tissues than in normal bone tissues, the miR-205 was negatively correlated with TGF-alpha levels in both OS and normal bone tissues. Functional studies demonstrated that miR-205 significantly decreased the capability of cell proliferation, invasion and migration and induced G(0)/G(1) growth arrest and apoptosis in OS cells. By using bioinformatics analytic tool (Targetscan), the 3'UTR of TGF-alpha gene was found to be a target of miR-205. Luciferase report assay further confirmed that TGF-alpha 3'UTR is a direct target of miR-205. We also found that the expression of TGF-alpha mRNA and protein was significantly down-regulated or up-regulated after miR-205 mimic or miR-205 inhibitor transfection. TGF-alpha knockdown study further showed that miR-205 regulated cell proliferation, invasion and migration by targeting TGF-alpha in OS. Enforced expression of TGF-alpha sufficiently restore the effects of miR-205 on cell proliferation, invasion and migration. In conclusion, our study suggested that miR-205 may function as a tumor suppressor via targeting TGF-alpha in OS, and the abnormal expression of miR-205 might be a key factor in OS progression. (C) 2015 Elsevier Inc. All rights reserved.
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