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微小 RNA-874 的异位表达通过 CCNE1 抑制胆管癌细胞上皮间质转化及 NF-κB 通路。

Ectopic expression of microRNA-874 represses epithelial mesenchymal transition through the NF-κB pathway via CCNE1 in cholangiocarcinoma.

机构信息

Interventional Department, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, PR China.

Interventional Department, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, PR China.

出版信息

Cell Signal. 2021 Jun;82:109927. doi: 10.1016/j.cellsig.2021.109927. Epub 2021 Jan 19.

Abstract

Cholangiocarcinoma (CC) is a devastating disease associated with poor survival rate. microRNAs (miRNAs) have recently been reported to assume a great role in CC development. This research aims to explore the functions of miR-874 in regulating epithelial mesenchymal transition (EMT) in CC. In obtained CC tissues and cells, miR-784 expression was assessed by RT-qPCR, and CCNE1 expression by RT-qPCR or immunohistochemistry. Dual-luciferase reporter assay was implemented for relationship between miR-784 and CCNE1. The roles of miR-784, CCNE1 and the NF-κB pathway in CC were investigated on human CC cell lines. CCNE1 was found to be highly expressed in CC while miR-874 expression was lowered in CC tissues and cells, thereby suggesting a negative regulatory effect of CCNE1. In QBC939 and RBE cells, overexpressing miR-874 or silencing CCNE1 led to augmented IκBα and E-cadherin expression, but diminished CCNE1, NF-κB, N-cadherin, and Vimentin expression. Moreover, overexpression of miR-874 or CCNE1 silencing led to reduced cell proliferation, invasion, and migration capabilities. In conclusion, we demonstrated that miR-874 negatively regulated CCNE1 to inhibit the NF-κB pathway, thus consequently suppressing EMT in CC. Therefore, the overexpression of miR-874 might bring favorable outcomes for the treatment of CC.

摘要

胆管癌 (CC) 是一种预后不良的破坏性疾病。microRNAs (miRNAs) 最近被报道在 CC 发展中发挥重要作用。本研究旨在探讨 miR-874 在调节 CC 上皮间质转化 (EMT) 中的功能。通过 RT-qPCR 评估获得的 CC 组织和细胞中的 miR-784 表达,通过 RT-qPCR 或免疫组织化学评估 CCNE1 表达。通过双荧光素酶报告基因实验验证 miR-784 与 CCNE1 之间的关系。在人 CC 细胞系中研究了 miR-784、CCNE1 和 NF-κB 通路在 CC 中的作用。发现 CCNE1 在 CC 中高表达,而 miR-874 在 CC 组织和细胞中表达降低,提示 CCNE1 的负调控作用。在 QBC939 和 RBE 细胞中,过表达 miR-874 或沉默 CCNE1 导致 IκBα 和 E-cadherin 表达增加,但 CCNE1、NF-κB、N-cadherin 和 Vimentin 表达减少。此外,过表达 miR-874 或沉默 CCNE1 导致细胞增殖、侵袭和迁移能力降低。总之,我们证明 miR-874 负调控 CCNE1 抑制 NF-κB 通路,从而抑制 CC 中的 EMT。因此,miR-874 的过表达可能为 CC 的治疗带来有利结果。

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