miR-483-5p Promotes Invasion and Metastasis of Lung Adenocarcinoma by Targeting RhoGDI1 and ALCAM
miR-483-5p Promotes Invasion and Metastasis of Lung Adenocarcinoma by Targeting RhoGDI1 and ALCAM
复制标题
miR-483-5p通过靶向RhoGDI1和ALCAM促进肺腺癌的侵袭和转移
DOI：
10.1158/0008-5472.can-13-2193
复制
发表时间：
2014-06-01
期刊：
影响因子：
11.2
通讯作者：
Bai, Xiaochun
中科院分区：
文献类型：
--
作者：
Song, Qiancheng;Xu, Yuanfei;Bai, Xiaochun
微小RNA（miRNA）在转移性癌症中的节点调节特性可能为治疗控制提供新的靶点。在这里，我们报告了miR-483 - 5p的上调与人肺腺癌的进展相关。miR-483 - 5p促进上皮-间质转化（EMT），伴随肺腺癌的侵袭和转移特性。从机制上讲，miR-483 - 5p被WNT/β-连环蛋白信号通路激活，并通过直接靶向Rho GDP解离抑制剂α（RhoGDI1）和活化的白细胞粘附分子（ALCAM）（两种假定的转移抑制因子）发挥其促转移功能。此外，我们发现RhoGDI1的下调增强Snail的表达，从而促进EMT。重要的是，miR-483 - 5p水平与β-catenin表达呈正相关，但与人肺腺癌中RhoGDI1和ALCAM水平呈负相关。我们的研究结果表明，miR-483 - 5p是一个关键的β-catenin激活的促转移miRNA和转移抑制因子RhoGDI1和ALCAM的负调节因子。(C)2014年AACR。
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/beta-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 beta-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 beta-catenin-activated prometastatic miRNA and a negative regulator of the metastasis suppressors RhoGDI1 and ALCAM. (C) 2014 AACR.