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Ectopic expression of microRNA-874 represses epithelial mesenchymal transition through the NF-κB pathway via CCNE1 in cholangiocarcinoma
Cellular Signalling ( IF 4.8 ) Pub Date : 2021-01-19 , DOI: 10.1016/j.cellsig.2021.109927
Xin Pan 1 , Gang Wang 1 , Baoming Wang 1
Affiliation  

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.



中文翻译:

microRNA-874的异位表达抑制胆管癌中通过CCNE1通过NF-κB通路的上皮间质转化

胆管癌 (CC) 是一种与低存活率相关的毁灭性疾病。最近有报道称 microRNA (miRNA) 在 CC 开发中发挥了重要作用。本研究旨在探讨 miR-874 在调节 CC 上皮间质转化 (EMT) 中的作用。在获得的 CC 组织和细胞中,通过 RT-qPCR 评估 miR-784 的表达,通过 RT-qPCR 或免疫组织化学评估 CCNE1 的表达。对 miR-784 和 CCNE1 之间的关系实施了双荧光素酶报告基因测定。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组织和细胞中的表达降低,从而表明CCNE1具有负调节作用。在 QBC939 和 RBE 细胞中,过表达 miR-874 或沉默 CCNE1 会导致 IκBα 和 E-cadherin 表达增加,但会降低 CCNE1、NF-κB、N-cadherin 和 Vimentin 的表达。此外,过表达 miR-874 或 CCNE1 沉默导致细胞增殖、侵袭和迁移能力降低。总之,我们证明了 miR-874 负调节 CCNE1 以抑制 NF-κB 通路,从而抑制 CC 中的 EMT。因此,miR-874的过表达可能为CC的治疗带来有利的结果。因此因此抑制了CC中的EMT。因此,miR-874的过表达可能为CC的治疗带来有利的结果。因此因此抑制了CC中的EMT。因此,miR-874的过表达可能为CC的治疗带来有利的结果。

更新日期:2021-03-01
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