Down-Regulation of miR-141 Induced by Helicobacter Pylori Promotes the Invasion of Gastric Cancer by Targeting STAT4

Down-Regulation of miR-141 Induced by Helicobacter Pylori Promotes the Invasion of Gastric Cancer by Targeting STAT4
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幽门螺杆菌诱导的miR-141下调通过靶向STAT4促进胃癌侵袭

DOI:
10.1159/000358671
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发表时间:
2014-01-01
影响因子:
--
通讯作者:
Zhang, Guoxin
Zhang, Guoxin
中科院分区:
医学1区
文献类型:
--
作者:
Zhou, Xiaoying;Xia, Yang;Zhang, Guoxin

文献摘要

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背景:幽门螺杆菌(Helicobacter pylori,Hp)感染与胃癌的相关性近年来得到证实.然而,其分子机制在很大程度上仍然未知。方法和结果:我们发现miR-141在幽门螺杆菌阳性标本(n = 75)中比阴性组织(n = 75)减少。miR-141的敲低增强了胃癌细胞的侵袭能力;同时,miR-141的过表达可以抑制胃癌细胞的体外侵袭能力。荧光素酶测定显示miR-141直接结合于STAT 4的3 '-非翻译区(3'-UTR)。通过qRT-PCR和western blot检测发现STAT 4在mRNA和蛋白水平上均上调。STAT 4的过表达用于模拟miR-141在胃癌侵袭中的作用。结论:miR-141可能通过调控STAT 4在胃癌侵袭过程中发挥重要作用,可能成为胃癌治疗的潜在靶点。
Background: The association between Helicobacter pylori infection and gastric cancer has been identified recently. However, the molecular mechanism remained largely unknown. Methods and Results: We found that miR-141 was decreased in Helicobacter pylori positive specimens (n=75) compared with negative tissues (n=75). The knockdown of miR-141 enhanced the invasion ability of gastric cancer cells; meanwhile, over-expression of miR-141 could inhibit the abilities of gastric cancer cells in vitro. A luciferase assay revealed that miR-141 was directly bound to the 3'-untranslated regions (3'-UTR) of STAT4. STAT4 was found up-regulated at mRNA and protein levels, as shown by qRT-PCR and western blot. Over-expression of STAT4 was used to mimic miR-141 action in the invasion of gastric cancer. Conclusion: MiR-141 may play a pivotal role in controlling gastric cancer invasion through regulating STAT4 and maybe a potential target to treat gastric cancer.