MicroRNA-331-3p inhibits epithelial-mesenchymal transition by targeting ErbB2 and VAV2 through the Rac1/PAK1/β-catenin axis in non-small-cell lung cancer.

作者: Xizhe Li , Jiali Zhu , Yuanqi Liu , Chaojun Duan , Ruimin Chang

DOI: 10.1111/CAS.14014

关键词:

摘要: MicroRNAs have been reported to play critical roles in the regulation of non-small-cell cancer (NSCLC) development, but role microRNA (miR)-331-3p NSCLC is still unclear. In this study, expression levels miR-331-3p tumor tissues and adjacent normal were examined by quantitative RT-PCR, relationship between patient clinicopathological characteristics was analyzed. The effects on epithelial-mesenchymal transition (EMT), migration, metastasis cells determined vitro vivo. Direct functional targets identified luciferase reporter assay, western blot immunohistochemical staining, rescue assay. downstream pathway regulated immunofluorescence, immunoprecipitation, Rac1 activity examination. Our results showed that significantly downregulated correlated with characteristics, could be an independent prognostic marker for patients. Furthermore, suppressed EMT, migration Both ErbB2 VAV2 direct miR-331-3p. activities Rac1, PAK1, β-catenin through targeting. These indicated suppresses migratory capacity, metastatic ability targeting Rac1/PAK1/β-catenin axis NSCLC.

参考文章(38)
Rui-Min Chang, Hao Yang, Feng Fang, Jiang-Feng Xu, Lian-Yue Yang, MicroRNA-331-3p promotes proliferation and metastasis of hepatocellular carcinoma by targeting PH domain and leucine-rich repeat protein phosphatase. Hepatology. ,vol. 60, pp. 1251- 1263 ,(2014) , 10.1002/HEP.27221
Lilly Y. W. Bourguignon, Hongbo Zhu, Bo Zhou, Falko Diedrich, Patrick A. Singleton, Mien-Chie Hung, Hyaluronan Promotes CD44v3-Vav2 Interaction with Grb2-p185HER2 and Induces Rac1 and Ras Signaling during Ovarian Tumor Cell Migration and Growth Journal of Biological Chemistry. ,vol. 276, pp. 48679- 48692 ,(2001) , 10.1074/JBC.M106759200
Idit Hornstein, Andres Alcover, Shulamit Katzav, Vav proteins, masters of the world of cytoskeleton organization. Cellular Signalling. ,vol. 16, pp. 1- 11 ,(2004) , 10.1016/S0898-6568(03)00110-4
Shizhen Emily Wang, Incheol Shin, Frederick Y. Wu, David B. Friedman, Carlos L. Arteaga, HER2/Neu (ErbB2) Signaling to Rac1-Pak1 Is Temporally and Spatially Modulated by Transforming Growth Factor β Cancer Research. ,vol. 66, pp. 9591- 9600 ,(2006) , 10.1158/0008-5472.CAN-06-2071
L S Havel, E R Kline, A M Salgueiro, A I Marcus, Vimentin regulates lung cancer cell adhesion through a VAV2-Rac1 pathway to control focal adhesion kinase activity Oncogene. ,vol. 34, pp. 1979- 1990 ,(2015) , 10.1038/ONC.2014.123
Francisco Romero, Siegmund Fischer, Structure and function of vav Cellular Signalling. ,vol. 8, pp. 545- 553 ,(1996) , 10.1016/S0898-6568(96)00118-0
Carlo M. Croce, Causes and consequences of microRNA dysregulation in cancer Nature Reviews Genetics. ,vol. 10, pp. 704- 714 ,(2009) , 10.1038/NRG2634
Narikazu Boku, HER2-positive gastric cancer. Gastric Cancer. ,vol. 17, pp. 1- 12 ,(2014) , 10.1007/S10120-013-0252-Z
Harsh Dweep, Carsten Sticht, Priyanka Pandey, Norbert Gretz, miRWalk - Database: Prediction of possible miRNA binding sites by walking the genes of three genomes Journal of Biomedical Informatics. ,vol. 44, pp. 839- 847 ,(2011) , 10.1016/J.JBI.2011.05.002