MiR-143-5p Deficiency Triggers EMT and Metastasis by Targeting HIF-1α in Gallbladder Cancer
MiR-143-5p Deficiency Triggers EMT and Metastasis by Targeting HIF-1α in Gallbladder Cancer
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MiR-143-5p 缺陷通过靶向胆囊癌中的 HIF-1 α 触发 EMT 和转移
DOI：
10.1159/000479903
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发表时间：
2017-01-01
影响因子：
--
通讯作者：
Wang, Jian
中科院分区：
文献类型：
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作者：
He, Min;Zhan, Ming;Wang, Jian
背景/目的：早期转移在胆囊癌（GBC）患者的肿瘤死亡中起着关键作用。越来越多的证据表明，miR-143- 5 p是参与癌症转移的积极参与者和潜在的治疗靶点。然而，其在GBC细胞发育中的作用仍不清楚。本研究旨在探讨miR-143- 5 p对胆囊癌细胞增殖和转移的抑制作用。方法：采用实时荧光定量PCR方法检测miR-143- 5 p及其靶基因HIF-1 α mRNA水平。免疫组化和western blot检测蛋白表达。通过MTS、集落形成、伤口愈合、transwell和荧光素酶报告基因分析证实了miR-143- 5 p的功能和调控机制。结果：首次发现miR-143- 5 p在胆囊癌组织中的表达明显低于相应的正常胆囊组织。此外，miR-143- 5 p缺陷与较大的肿瘤大小、晚期TNM分期和较差的生存率密切相关。在体外实验中，miR-143- 5 p显著抑制GBC细胞的增殖、迁移和侵袭，而miR-143- 5 p反义则产生相反的作用。进一步阐明其分子机制，我们发现miR-143- 5 p通过下调HIF-1 α的表达发挥其抑制作用，进而抑制Twist 1的表达，阻碍上皮-间质转化（EMT）。结论：总之，我们的研究发现了一种新的调控因子miR-143- 5 p，其通过靶向HIF-1 α/EMT相关信号通路参与GBC预后，可作为GBC的生物标志物和治疗靶点。(C)2017作者（s）由S. Karger AG，巴塞尔
Background/Aims: Early metastasis plays a pivotal role in tumor-caused death in gallbladder cancer (GBC) patients. Increasing evidence suggest that miR-143-5p is an active player involved in cancer metastasis and a potential therapeutic target. However, its role in the development of GBC cells remains unclear. The aim of this study is to reveal the inhibiting effects of miR-143-5p on the proliferation and metastasis in GBC. Methods: Quantitative real-time PCR were used to investigate miR-143-5p and its target HIF-1 alpha mRNA levels. Protein expression was measured by immunohistochemistry and western blot. The function and regulation mechanism of miR-143-5p was confirmed by MTS, colony formation, wound healing, transwell, and luciferase reporter assays. Results: miR-143-5p was first found significantly reduced in GBC tissues compared with corresponding noncancerous gallbladder tissues. In addition, miR-143-5p deficiency correlated well with larger tumor size, advanced TNM stage, and poorer survival rate. In vitro, miR-143-5p addition dramatically suppressed GBC cells proliferation, migration and invasion, whereas miR-143-5p antisense led the opposite effects. Further elucidating the molecular mechanism inside, we found miR-143-5p exerted its inhibitory function through downregulating the expression of HIF-1 alpha, which further reduced Twist1 and impeded epithelial-mesenchymal transition (EMT). Conclusions: Altogether, our studies identified a novel regulator, miR-143-5p, implicated in GBC prognosis through targeting HIF-1 alpha/EMT related signaling pathway, which could serve as a biomarker and therapeutic target for GBC. (C) 2017 The Author(s) Published by S. Karger AG, Basel