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微小RNA-125a-5p通过靶向转录激活子TAZ抑制结肠癌细胞的上皮-间质转化、侵袭和迁移。

miR-125a-5p inhibits colorectal cancer cell epithelial-mesenchymal transition, invasion and migration by targeting TAZ.

作者信息

Tang Lei, Zhou Li, Wu Shengchun, Shi Xiaoming, Jiang Guangwei, Niu Shuai, Ding Dianzhu

机构信息

Vascular Surgery, Hebei General Hospital, Shijiazhuang, Hebei 050000, People's Republic of China.

Department of Pneumology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, People's Republic of China.

出版信息

Onco Targets Ther. 2019 May 7;12:3481-3489. doi: 10.2147/OTT.S191247. eCollection 2019.

Abstract

miR-125a-5p regulated biological processes in various types of cancer, including colorectal cancer (CRC). TAZ, a vital transcriptional coactivators of the Hippo pathway, was found to be overexpressed in various cancers. This study aims to study the effect of miR-125a-5p on the progression of CRC by regulating TAZ expression. In this study, miR-125a-5p and TAZ expression in CRC tissue and cell lines were detected by real-time polymerase chain reaction (RT-PCR). Luciferase reporter assay was applied to detect whether TAZ was a target of miR-125a-5p. Cell migration and invasion were detected in vitro by wound-healing assay and cell invasion assay. Western blot was used to detect the expression of epithelial-mesenchymal transition (EMT)-related proteins. The results revealed downregulation of miR-125a-5p, as well as upregulation of TAZ in CRC tissue and cell lines. TAZ was identified as a direct target of miR-125a-5p, and its expression was negatively regulated by miR-125a-5p in CRC cell lines. The functional studies revealed that overexpression of miR-125a-5p inhibited the migration, invasion and EMT of CRC cells, while upregulation of TAZ reversed the inhibitory effect caused by miR-125a-5p. Our data suggest that miR-125a-5p inhibits CRC cell migration, invasion and EMT by targeting TAZ. These results suggest that miR-125a-5p serves as a potential therapeutic biomarker for CRC patients.

摘要

miR-125a-5p调控多种类型癌症中的生物学过程,包括结直肠癌(CRC)。TAZ是Hippo通路的一种重要转录共激活因子,在多种癌症中被发现过表达。本研究旨在通过调节TAZ表达来研究miR-125a-5p对结直肠癌进展的影响。在本研究中,通过实时聚合酶链反应(RT-PCR)检测了结直肠癌组织和细胞系中miR-125a-5p和TAZ的表达。应用荧光素酶报告基因检测法来检测TAZ是否为miR-125a-5p的靶标。通过伤口愈合试验和细胞侵袭试验在体外检测细胞迁移和侵袭。蛋白质免疫印迹法用于检测上皮-间质转化(EMT)相关蛋白的表达。结果显示,在结直肠癌组织和细胞系中miR-125a-5p表达下调,TAZ表达上调。TAZ被确定为miR-125a-5p的直接靶标,在结直肠癌细胞系中其表达受到miR-125a-5p的负调控。功能研究表明,miR-125a-5p过表达抑制了结直肠癌细胞的迁移、侵袭和EMT,而TAZ的上调逆转了miR-125a-5p引起的抑制作用。我们的数据表明,miR-125a-5p通过靶向TAZ抑制结直肠癌细胞的迁移、侵袭和EMT。这些结果表明,miR-125a-5p可作为结直肠癌患者潜在的治疗生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/319f/6511622/fd28d1f3aaad/OTT-12-3481-g0001.jpg

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