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

COUP-TFII promotes epithelial-mesenchymal transition by inhibiting miR-34a expression in colorectal cancer
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COUP-TFII 通过抑制结直肠癌中 miR-34a 的表达促进上皮间质转化

DOI:
10.3892/ijo.2019.4718
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发表时间:
2019-04-01
影响因子:
5.2
通讯作者:
Wang, Xiang
Wang, Xiang
中科院分区:
医学2区
文献类型:
--
作者:
Bao, Ying;Lu, Yongliang;Wang, Xiang

文献摘要

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鸡卵清蛋白上游启动子-转录因子II(COUP-TFII)表达在结直肠癌中上调,并与其进展和预后不良相关。本研究的目的是确定COUP-TFII是否通过抑制microRNA(miR)-34a来调节结直肠癌细胞(CRC)的侵袭和迁移。进行Transwell系统和伤口愈合测定以分别检查细胞侵袭和迁移。采用逆转录聚合酶链反应和蛋白质印迹法分别检测靶分子的RNA和蛋白水平。结果显示,COUP-TFII敲低显著抑制CRC侵袭和迁移。此外,一种众所周知的肿瘤抑制因子miR-34 a的表达与COUP-TFII表达呈负相关。miR-34 a模拟物显著降低CRC侵袭和迁移能力,而miR-34 a抑制剂增强CRC侵袭和迁移活性。在COUP-TFII敲低后,阴性小干扰RNA和miR-34 a抑制剂组之间没有显著差异。Western blotting结果显示,miR-34 a模拟物可抑制CRCs的上皮-间充质转化(EMT)过程,而miR-34 a抑制剂则相反。总而言之,结果表明,通过研究COUP-TFII调节EMT的机制,miR-34 a调节CRC侵袭和迁移。
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.