miR-483-5p promotes invasion and metastasis of lung adenocarcinoma by targeting RhoGDI1 and ALCAM.
By: Qiancheng Song, Yuanfei Xu, Cuilan Yang, Zhenguo Chen, Chunhong Jia, Juan Chen, Yue Zhang, Pinglin Lai, Xiaorong Fan, Xuan Zhou, Jun Lin, Ming Li, Wenli Ma, Shenqiu Luo, Xiaochun Bai

Authors' Affiliations: Department of Cell Biology, School of Basic Medical Sciences; and Institute of Genetic Engineering, Southern Medical University, Guangzhou, China.
2014-4-7; doi: 10.1158/0008-5472.CAN-13-2193
Abstract

The nodal regulatory properties of microRNAs (miRNA) in metastatic cancer may offer new targets for therapeutic control. Here, we report that upregulation of miR-483-5p is correlated with the progression of human lung adenocarcinoma. miR-483-5p promotes the epithelial-mesenchymal transition (EMT) accompanied by invasive and metastatic properties of lung adenocarcinoma. Mechanistically, miR-483-5p is activated by the WNT/β-catenin signaling pathway and exerts its prometastatic function by directly targeting the Rho GDP dissociation inhibitor alpha (RhoGDI1) and activated leukocyte cell adhesion molecule (ALCAM), two putative metastasis suppressors. Furthermore, we found that downregulation of RhoGDI1 enhances expression of Snail, thereby promoting EMT. Importantly, miR-483-5p levels are positively correlated with β-catenin expression, but are negatively correlated with the levels of RhoGDI1 and ALCAM in human lung adenocarcinoma. Our findings reveal that miR-483-5p is a critical β-catenin-activated prometastatic miRNA and a negative regulator of the metastasis suppressors RhoGDI1 and ALCAM.



©2014 American Association for Cancer Research.

PMID:24710410






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