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microRNA-495 的过表达通过靶向高迁移率族核小体结合域 5 抑制骨肉瘤细胞的增殖、侵袭并诱导其凋亡。

Overexpression of microRNA-495 suppresses the proliferation and invasion and induces the apoptosis of osteosarcoma cells by targeting high-mobility group nucleosome-binding domain 5.

机构信息

Department of Orthopaedics, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.

Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130031, P.R. China.

出版信息

Oncol Rep. 2017 Aug;38(2):1099-1107. doi: 10.3892/or.2017.5715. Epub 2017 Jun 13.

Abstract

It has been suggested that microRNAs (miRNAs) act as critical regulators in tumorigenesis. MicroRNA-495 (miR-495) has been suggested as a cancer-associated miRNA in various types of cancers; however, the role of miR-495 in osteosarcoma is unknown. The aim of the present study was to determine whether miR-495 is involved in osteosarcoma, and to investigate the potential molecular mechanism of its involvement. We found that miR-495 was significantly downregulated in osteosarcoma tissues and cell lines, as detected by real-time quantitative polymerase chain reaction (RT-qPCR). Overexpression of miR-495 inhibited osteosarcoma cell proliferation in 3-(4,5-dimethylthiazol-2-yl)- ,5-diphenyltetrazolium bromide, colony formation and cell cycle assays. Overexpression of miR-495 induced osteosarcoma cell apoptosis. Moreover, miR-495 overexpression also inhibited osteosarcoma cell invasion. Bioinformatics and luciferase reporter assays demonstrated that miR-495 targets the 3'-untranslated region of high-mobility group nucleosome‑binding domain 5 (HMGN5), a potential oncogene in various types of cancers. Overexpression of miR-495 inhibited the expression of HMGN5, cyclin B1, Bcl-2 and matrix metalloproteinase 9. In addition, restoration of HMGN5 protein expression abrogated the miR-495-induced effects. Taken together, the present study indicated that miR-495 suppresses the proliferation and invasion and induces the apoptosis of osteosarcoma cells by targeting HMGN5, providing a novel insight into the molecular pathogenesis of osteosarcoma and suggesting a potential molecular target for the development of an miRNA-targeted therapeutic strategy for osteosarcoma.

摘要

有人提出 microRNAs(miRNAs)在肿瘤发生中起关键调节作用。MicroRNA-495(miR-495)已被认为是各种类型癌症中的癌相关 miRNA;然而,miR-495 在骨肉瘤中的作用尚不清楚。本研究旨在确定 miR-495 是否参与骨肉瘤,并探讨其参与的潜在分子机制。我们发现 miR-495 在骨肉瘤组织和细胞系中显著下调,实时定量聚合酶链反应(RT-qPCR)检测结果显示。miR-495 的过表达抑制了 3-(4,5-二甲基噻唑-2-基)-5-二苯基四唑溴盐(MTT)测定、集落形成和细胞周期测定中的骨肉瘤细胞增殖。miR-495 的过表达诱导骨肉瘤细胞凋亡。此外,miR-495 的过表达还抑制了骨肉瘤细胞的侵袭。生物信息学和荧光素酶报告基因检测表明,miR-495 靶向高迁移率族核小体结合域 5(HMGN5)的 3'-非翻译区,HMGN5 是各种类型癌症中的潜在癌基因。miR-495 的过表达抑制了 HMGN5、细胞周期蛋白 B1、Bcl-2 和基质金属蛋白酶 9 的表达。此外,HMGN5 蛋白表达的恢复消除了 miR-495 诱导的作用。综上所述,本研究表明 miR-495 通过靶向 HMGN5 抑制骨肉瘤细胞的增殖和侵袭,并诱导其凋亡,为骨肉瘤的分子发病机制提供了新的见解,并为开发针对骨肉瘤的 miRNA 靶向治疗策略提供了潜在的分子靶点。

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