MicroRNA-133a, downregulated in osteosarcoma, suppresses proliferation and promotes apoptosis by targeting Bcl-xL and Mcl-1
MicroRNA-133a, downregulated in osteosarcoma, suppresses proliferation and promotes apoptosis by targeting Bcl-xL and Mcl-1
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MicroRNA-133a 在骨肉瘤中下调，通过靶向 Bcl-xL 和 Mcl-1 抑制增殖并促进细胞凋亡
DOI：
10.1016/j.bone.2013.05.020
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发表时间：
2013-09-01
期刊：
影响因子：
4.1
通讯作者：
Tang, Hao
中科院分区：
文献类型：
--
作者：
Ji, Fang;Zhang, Hao;Tang, Hao
去调控的microRNAs及其在癌症发展中的作用引起了人们的极大关注。虽然miR-133a已被证明在成骨过程中起重要作用，但其在骨肉瘤发生和发展中的作用仍不清楚。因此，本研究重点研究miR-133a在骨肉瘤发生发展过程中的表达及其机制。我们发现miR-133a在骨肉瘤细胞系和原代人骨肉瘤组织中表达下调，并且其表达下调与患者的肿瘤进展和预后密切相关。功能研究表明，修复miR-133a可以抑制骨肉瘤细胞系的增殖，促进细胞凋亡，抑制成瘤性。进一步通过生物信息学预测和实验验证筛选miR-133a的靶基因，结果表明miR-133a的抗肿瘤作用可能是通过靶向和抑制Bclxl和Mcl-1的表达实现的。综上所述，我们的数据阐明了miR-133a在骨肉瘤发病机制中的作用，并暗示了其在癌症治疗中的潜力。Crown版权所有(C)2013由Elsevier Inc.出版。保留所有权利。
Deregulated microRNAs and their roles in cancer development have attracted much attention. Although miR-133a has been shown to be important in osteogenesis, its roles in osteosarcoma carcinogenesis and progression remain unknown. Hence, we focused on the expression and mechanisms of miR-133a in osteosarcoma development in this study. We found that miR-133a was downregulated in osteosarcoma cell lines and primary human osteosarcoma tissues, and its decrease was significantly correlated with tumor progression and prognosis of the patients. Functional studies revealed that restoration of miR-133a could reduce cell proliferation, promote cell apoptosis, and suppress tumorigenicity in osteosarcoma cell lines. Furthermore, bio-informatic prediction and experimental validation were applied to identify target genes of miR-133a, and the results revealed that the anti-tumor effect of miR-133a was probably due to targeting and repressing of Bcl-xL and Mcl-1 expression. Taken together, our data elucidate the roles of miR-133a in osteosarcoma pathogenesis and implicate its potential in cancer therapy. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved.