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Overexpression of miR-92a promotes the tumor growth of osteosarcoma by suppressing F-box and WD repeat-containing protein 7.

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机构: [1]Department of Orthopedics, Huzhou Central Hospital, Huzhou, Zhejiang 313003, China [2]Department of Orthopedics, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, China [3]Department of Orthopedics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China
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关键词: miR-92a Osteosarcoma FBXW7 Proliferation Cell cycle progression Apoptosis

摘要:
MicroRNAs (miRNAs) have been reported to be critical players in osteosarcoma (OS). Among numerous cancer-related miRNAs, the expression level of miR-92a and its potential role in OS has not been investigated. Here, We showed that overexpression of miR-92a was identified in OS specimens and cells compared to normal bone tissues. The high level of miR-92a was correlated with high T classification and advanced clinical stages of OS patients. Notably, miR-92a highly expressing OS patients showed a notably reduced survival rate. In vitro experiments showed that loss of miR-92a inhibited U2OS cell proliferation and cell-cycle progression while induced apoptosis. In turn, its restoration facilitated MG-63 cell growth and suppressed apoptosis. Experimental nude mice showed that miR-92a silencing prohibited the in vivo growth of OS cells. Furthermore, bioinformatics software predicted that F-box and WD repeat-containing protein 7 (FBXW7) was a direct target of miR-92a. We then observed the negative regulation of miR-92a on FBXW7 expression and the direct binding between them was further verified by dual-luciferase assays in OS cells. Forced expression of FBXW7 resulted in reduced proliferation, cell cycle arrest at G1 phase and increased apoptosis in miR-92a overexpressing MG-63 cells. In summary, this study demonstrates miR-92a probably functions as a driver of tumor progression by targeting FBXW7, and highlights the potential effects of miR-92a on prognosis and treatment of OS. Copyright © 2017. Published by Elsevier B.V.

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出版当年[2016]版:
大类 | 3 区 生物
小类 | 4 区 遗传学
最新[2025]版:
大类 | 3 区 生物学
小类 | 3 区 遗传学
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第一作者机构: [1]Department of Orthopedics, Huzhou Central Hospital, Huzhou, Zhejiang 313003, China
通讯作者:
通讯机构: [1]Department of Orthopedics, Huzhou Central Hospital, Huzhou, Zhejiang 313003, China [3]Department of Orthopedics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China [*1]Department of Orthopedics, Huzhou Central Hospital, 198 Hongqi Road, Huzhou, Zhejiang 313003, China [*2]Department of Orthopedics, School of Traditional Chinese Medicine, Southern Medical University, 1838 Guangzhou Road North, Guangzhou, Guangdong 510515, China
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