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miR-138-5p 通过靶向人视网膜母细胞瘤中的丙酮酸脱氢酶激酶 1 发挥肿瘤抑制作用。

Mir-138-5p acts as a tumor suppressor by targeting pyruvate dehydrogenase kinase 1 in human retinoblastoma.

机构信息

Department of Ophthalmology, Fuzhou Second Hospital, Fujian, China.

出版信息

Eur Rev Med Pharmacol Sci. 2017 Dec;21(24):5624-5629. doi: 10.26355/eurrev_201712_14005.

Abstract

OBJECTIVE

MicroRNAs have caught more attention for their role in tumor progression. Retinoblastoma (RB) is one of these ordinary malignant tumors. This study aims to identify whether mir-138-5p can regulate the development of RB, and find out its potential mechanism.

MATERIALS AND METHODS

Mir-138-5p expression in RB cells was monitored by RT-qPCR. Besides, the role of mir-138-5p in RB development was explored through function experiments in vitro. The potential mechanism was further explored by RT-qPCR, luciferase assay, and Western blot assay.

RESULTS

In our investigation, mir-138-5p was lower-expressed in RB cells than that in retinal pigment epithelial cells. Moreover, overexpression of mir-138-5p repressed cell viability, migration and invasion, and induced apoptosis of RB cells, while downregulated mir-138-5p increased cell viability, migration and invasion, and reduced apoptosis of RB cells. Furthermore, pyruvate dehydrogenase kinase 1 (PDK1) could be downregulated via overexpression of mir-138-5p, while PDK1 was upregulated via knockdown of mir-138-5p.

CONCLUSIONS

Our results suggested that mir-138-5p could repress the development of RB via suppressing PDK1, which may offer a new vision for interpreting the mechanism of RB tumorigenesis.

摘要

目的

微小 RNA 在肿瘤进展中的作用引起了更多的关注。视网膜母细胞瘤(RB)就是这些常见的恶性肿瘤之一。本研究旨在确定 mir-138-5p 是否可以调节 RB 的发展,并找出其潜在的机制。

材料和方法

通过 RT-qPCR 监测 RB 细胞中 mir-138-5p 的表达。此外,通过体外功能实验探讨了 mir-138-5p 在 RB 发育中的作用。通过 RT-qPCR、荧光素酶测定和 Western blot 测定进一步探讨了潜在的机制。

结果

在我们的研究中,RB 细胞中的 mir-138-5p 表达低于视网膜色素上皮细胞。此外,mir-138-5p 的过表达抑制 RB 细胞的活力、迁移和侵袭,并诱导细胞凋亡,而 mir-138-5p 的下调则增加 RB 细胞的活力、迁移和侵袭,并减少细胞凋亡。此外,丙酮酸脱氢酶激酶 1(PDK1)可以通过过表达 mir-138-5p 下调,而通过下调 mir-138-5p 上调 PDK1。

结论

我们的结果表明,mir-138-5p 可以通过抑制 PDK1 来抑制 RB 的发展,这可能为解释 RB 肿瘤发生的机制提供了新的视角。

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