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微小 RNA-203 通过靶向 Runt 相关转录因子 2 抑制骨肉瘤细胞的增殖、侵袭,促进其凋亡。

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

机构信息

Department of Orthopedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.

Department of Orthopedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.

出版信息

Biomed Pharmacother. 2017 Jul;91:1075-1084. doi: 10.1016/j.biopha.2017.05.034. Epub 2017 May 15.

Abstract

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.

摘要

越来越多的证据表明,微小 RNA-203(miR-203)在许多人类肿瘤组织中异常表达,并且与人类肿瘤的发生、发展和临床结局密切相关。本研究旨在确定 miR-203 在骨肉瘤细胞中的靶基因和功能意义。我们发现 miR-203 在骨肉瘤组织和细胞(MG63 和 U2-OS)中的表达低于相邻正常组织和正常成骨细胞(hFOB1.19)。体外研究进一步表明,外源性 miR-203 过表达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,miR-203 调节凋亡、细胞周期和侵袭相关蛋白。我们的研究结果还揭示了 runt 相关转录因子 2(RUNX2)是 miR-203 的直接负调控因子。这些结果表明,miR-203 可能作为一种肿瘤抑制因子发挥作用,因此在治疗人类骨肉瘤方面可能具有潜在的治疗作用。

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