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COUP‑TFII 通过抑制结直肠癌细胞中 miR‑34a 的表达促进上皮‑间充质转化。

COUP‑TFII promotes epithelial‑mesenchymal transition by inhibiting miR‑34a expression in colorectal cancer.

机构信息

First Affiliated Hospital, Huzhou University, The First People's Hospital of Huzhou, Huzhou, Zhejiang 313000, P.R. China.

Department of Medicine, Huzhou University, Huzhou, Zhejiang 313000, P.R. China.

出版信息

Int J Oncol. 2019 Apr;54(4):1337-1344. doi: 10.3892/ijo.2019.4718. Epub 2019 Feb 18.

DOI:10.3892/ijo.2019.4718
PMID:30968145
Abstract

Chicken ovalbumin upstream promoter‑transcription factor II (COUP‑TFII) expression is upregulated in colorectal cancer and is associated with its progression and a poor prognosis. The aim of the present study was to determine whether COUP‑TFII regulates colorectal cancer cell (CRC) invasion and migration by inhibiting microRNA (miR)‑34a. Transwell system and wound healing assays were performed to examine cell invasiveness and migration, respectively. Reverse transcription polymerase chain reaction and western blotting were used to detect the RNA and protein levels of target molecules, respectively. The results revealed that COUP‑TFII knockdown significantly inhibited CRC invasion and migration. In addition, the expression of miR‑34a, a well‑known tumor suppressor was revealed to be inversely correlated with COUP‑TFII expression. The miR‑34a mimic significantly reduced CRC invasion and migration abilities, while the miR‑34a inhibitor enhanced CRC invasion and migration activity. There was no significant difference between the negative small interfering RNA and miR‑34a inhibitor groups following knockdown of COUP‑TFII. Furthermore, western blotting demonstrated that miR‑34a mimics inhibited the epithelial‑mesenchymal transition (EMT) process of CRCs, while the miR‑34a inhibitor had the opposite effect. Taken together, the results demonstrate that miR‑34a regulates CRC invasion and migration by examining the mechanism by which COUP‑TFII regulates EMT.

摘要

鸡卵清蛋白上游启动子转录因子 II(COUP-TFII)在结直肠癌中的表达上调,并与肿瘤的进展和预后不良相关。本研究旨在通过抑制 microRNA(miR)-34a 来确定 COUP-TFII 是否调节结直肠癌细胞(CRC)的侵袭和迁移。采用 Transwell 系统和划痕愈合试验分别检测细胞侵袭和迁移。逆转录聚合酶链反应和蛋白质印迹法分别用于检测靶分子的 RNA 和蛋白水平。结果表明,COUP-TFII 敲低显著抑制 CRC 的侵袭和迁移。此外,miR-34a 的表达与 COUP-TFII 的表达呈负相关,miR-34a 是一种公认的肿瘤抑制因子。miR-34a 模拟物显著降低 CRC 的侵袭和迁移能力,而 miR-34a 抑制剂增强 CRC 的侵袭和迁移活性。COUP-TFII 敲低后,阴性小干扰 RNA 组与 miR-34a 抑制剂组之间无显著差异。此外,蛋白质印迹法表明,miR-34a 模拟物抑制 CRC 的上皮-间充质转化(EMT)过程,而 miR-34a 抑制剂则具有相反的作用。综上所述,这些结果表明,miR-34a 通过检查 COUP-TFII 调节 EMT 的机制来调节 CRC 的侵袭和迁移。

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