MicroRNA-203 inhibits proliferation and invasion, and promotes apoptosis of osteosarcoma cells by targeting Runt-related transcription factor 2

MicroRNA-203 inhibits proliferation and invasion, and promotes apoptosis of osteosarcoma cells by targeting Runt-related transcription factor 2
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DOI:
10.1016/j.biopha.2017.05.034
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发表时间:
2017-07-01
影响因子:
7.5
通讯作者:
Lv, Chen
Lv, Chen
中科院分区:
医学2区
文献类型:
--
作者:
Lin, Wenjun;Zhu, Xiongbai;Lv, Chen

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越来越多的证据表明,microRNA-203(miR-203)在许多人类肿瘤组织中异常表达,并与人类肿瘤的发生、发展和临床结局显着相关。本研究的目的是确定骨肉瘤细胞中miR-203的靶基因和功能意义。我们发现,与邻近正常组织和正常成骨细胞(hFOB1.19)相比,骨肉瘤组织和细胞(MG63和U2-OS)中miR-203的表达分别降低。体外研究进一步表明,外源性miR-203过表达可抑制骨肉瘤细胞增殖和侵袭,并促进细胞凋亡。在分子水平上,我们的结果证实了细胞凋亡、细胞周期和侵袭相关蛋白受到miR-203的调节。我们的研究结果还表明,Runt 相关转录因子 2 (RUNX2) 直接受到 miR-203 的负调控。这些结果表明 miR-203 可能起到肿瘤抑制因子的作用,因此可能具有治疗人类骨肉瘤的潜力。 (C) 2017 Elsevier Masson SAS。版权所有。
Accumulating evidence indicates that microRNA-203 (miR-203) is abnormally expressed in many human tumor tissues and significantly associated with the occurrence, development and clinical outcomes of human tumors. The aim of this study was to determine the target genes and functional significance of miR-203 in osteosarcoma cells. We found reduced expression of miR-203 in osteosarcoma tissues and cells (MG63 and U2-OS) compared with the adjacent normal tissues and normal osteoblastic cells (hFOB1.19), respectively. In vitro studies further demonstrated that exogenous miR-203 overexpression inhibited osteosarcoma cell proliferation and invasion, and promoted apoptosis. At the molecular level, our results confirmed that apoptosis, cell cycle and invasion-related proteins were regulated by miR-203. Our findings also revealed that Runt-related transcription factor 2 (RUNX2) was directly negatively regulated by miR-203. These results suggested that miR-203 may function as a tumor suppressor and may therefore have therapeutic potential in the treatment of human osteosarcoma. (C) 2017 Elsevier Masson SAS. All rights reserved.