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微小 RNA-137 的下调通过调节 COX-2/PGE2 信号通路促进视网膜母细胞瘤细胞的增殖和侵袭。

The down-regulation of microRNA-137 contributes to the up-regulation of retinoblastoma cell proliferation and invasion by regulating COX-2/PGE2 signaling.

机构信息

Department of Ophthalmology, Shaanxi Provincial People's Hospital, Xi'an, 710068, China.

Department of Obstetrics, The First Affiliated Hospital of Xi'an Medical University, Xi'an, 710077, China.

出版信息

Biomed Pharmacother. 2018 Oct;106:35-42. doi: 10.1016/j.biopha.2018.06.099. Epub 2018 Jun 23.

Abstract

MicroRNA-137 (miR-137) plays an important role in the development and progression of many types of human cancers; however, the role of miR-137 in retinoblastoma (RB) remains unclear. In this study, we aimed to investigate the functional significance and molecular mechanisms of miR-137 in RB. We reported that miR-137 was frequently down-regulated in RB tissues and cell lines. The overexpression of miR-137 inhibited RB cell proliferation and invasion, while the suppression of miR-137 promoted RB cell proliferation and invasion. Bioinformatic analysis predicted that cyclooxygenase-2 (COX-2) was a potential target gene of miR-137, which was validated by a dual-luciferase reporter assay. Moreover, our results showed that miR-137 negatively regulated the expression of COX-2 and the production of prostaglandin E2 (PGE2) in RB cells. The knockdown of COX-2 suppressed the proliferation and invasion of RB cells as well as the production of PGE2. The overexpression of COX-2 significantly reversed the inhibitory effect of miR-137 overexpression on RB cell proliferation and invasion. Taken together, these results suggest that miR-137 suppresses the proliferation and invasion of RB cells by targeting COX-2/PGE2. Our study reveals a tumor suppressive role of miR-137 in the progression of RB and suggests miR-137 as a potentially effective therapeutic target for the treatment of RB.

摘要

microRNA-137 (miR-137) 在多种人类癌症的发生和发展中发挥着重要作用;然而,miR-137 在视网膜母细胞瘤 (RB) 中的作用尚不清楚。在本研究中,我们旨在探讨 miR-137 在 RB 中的功能意义和分子机制。我们报道 miR-137 在 RB 组织和细胞系中经常下调。miR-137 的过表达抑制 RB 细胞增殖和侵袭,而 miR-137 的抑制促进 RB 细胞增殖和侵袭。生物信息学分析预测环氧化酶-2 (COX-2) 是 miR-137 的一个潜在靶基因,这通过双荧光素酶报告基因实验得到了验证。此外,我们的结果表明 miR-137 负调控 COX-2 的表达和 RB 细胞中前列腺素 E2 (PGE2) 的产生。COX-2 的敲低抑制了 RB 细胞的增殖和侵袭以及 PGE2 的产生。COX-2 的过表达显著逆转了 miR-137 过表达对 RB 细胞增殖和侵袭的抑制作用。综上所述,这些结果表明 miR-137 通过靶向 COX-2/PGE2 抑制 RB 细胞的增殖和侵袭。我们的研究揭示了 miR-137 在 RB 进展中的肿瘤抑制作用,并表明 miR-137 可能是治疗 RB 的潜在有效治疗靶点。

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