miR-664a-3p functions as an oncogene by targeting Hippo pathway in the development of gastric cancer
miR-664a-3p functions as an oncogene by targeting Hippo pathway in the development of gastric cancer
复制标题
miR-664a-3p通过靶向Hippo通路作为胃癌发展中的癌基因
DOI：
10.1111/cpr.12567
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发表时间：
2019-05-01
影响因子：
8.5
通讯作者：
Xu, Zekuan
中科院分区：
文献类型：
--
作者：
Wang, Lu;Li, Bowen;Xu, Zekuan
目的miR-664 a-3 p在多种恶性肿瘤中具有不同的功能，但其在胃癌中的确切作用及其机制尚不清楚。本研究旨在探讨miR-664 a-3 p在胃癌发生发展中的作用。方法采用qRT-PCR方法检测胃癌组织和细胞中miR-664 a-3 p的表达。采用细胞增殖实验和transwell实验检测miR-664 a-3 p对胃癌细胞增殖的影响。采用免疫印迹和免疫荧光技术检测上皮间质转化（EMT）相关蛋白和信号通路。采用生物信息学、双荧光素酶测定或ChIP测定来鉴定miR-664 a-3 p与其靶基因或Foxp 3之间的相互作用。通过小鼠致瘤性模型研究体内效应。结果胃癌组织和细胞中miR-664 a-3 p表达频繁上调。miR-664 a-3 p的高表达显著促进体外和体内的增殖和侵袭。MOB 1A被证实是miR-664 a-3 p的靶点，并且MOB 1A的恢复减弱了miR-664 a-3 p的作用。一系列研究表明miR-664 a-3 p参与EMT过程，并通过下调MOB 1A使Hippo通路失活。结论miR-664 a-3 p在胃癌的发生发展过程中可能通过靶向Hippo通路发挥癌基因作用。
Objectives It has been accounted that miR-664a-3p has different functions in several malignancies; however, the precise role and underlying mechanism in gastric cancer have not been elucidated. Our study aims to explore the function of miR-664a-3p on the progression of gastric cancer (GC). Methods qRT-PCR was applied to detect the expression of miR-664a-3p in GC tissues and cells. The functions of miR-664a-3p on GC in vitro were examined by cell proliferation assay, and transwell assay. Related proteins of epithelial-mesenchymal transition (EMT) and signal pathway were evaluated by Western blot and immunofluorescence analysis. The bioinformatic, dual-luciferase assay or ChIP assay were employed to identify the interaction between miR-664a-3p and its target gene or Foxp3. The effects in vivo were investigated through a mouse tumorigenicity model. Results miR-664a-3p was frequently upregulated in GC tissues and cells. Elevated expression of miR-664a-3p significantly promoted proliferation and invasion in vitro and in vivo. MOB1A was confirmed to be a target of miR-664a-3p and restoration of MOB1A attenuated the effects of miR-664a-3p. A series of investigations indicated that miR-664a-3p contributed to EMT process and inactivated the Hippo pathway by downregulating MOB1A. Conclusion Taken together, we revealed that miR-664a-3p functions as an oncogene by targeting Hippo pathway in the development of gastric cancer.