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