Qiu Yinghe, Luo Xiangji, Kan Tong, Zhang Yongjie, Yu Wenlong, Wei Yongpeng, Shen Ningjia, Yi Bin, Jiang Xiaoqing
The Second Department of Biliary Tract Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medicine University, 225 Changhai Road, Shanghai 200438, China.
Mol Biosyst. 2014 Mar 4;10(3):679-85. doi: 10.1039/c3mb70479c. Epub 2014 Jan 21.
Transforming growth factor β (TGF-β) plays important roles in tumor metastasis by regulating miRNAs expression. miR-182 is an important molecule in the regulation of cancer progression. The aim of the study is to assess the role of miR-182 in TGF-β-induced cancer metastasis. In the present study, we found that miR-182 levels are significantly upregulated in GBC tissues compared with normal controls, and miR-182 expression is remarkably increased in primary tumors that subsequently metastasized, when compared to those primary tumors that did not metastasize. TGF-β induces miR-182 expression in GBC cells, and overexpression of miR-182 promotes GBC cell migration and invasion, whereas miR-182 inhibition suppresses TGF-β-induced cancer cell migration and invasion. The blockage of miR-182 by a specific inhibitor effectively inhibits pulmonary metastases in vivo. We further identified that the cell adhesion molecule1 (CADM1) is a new target gene of miR-182. miR-182 negatively regulates CADM1 expression in vitro and in vivo. Importantly, re-expression of CADM1 in GBC cells partially abrogates miR-182-induced cell invasion.
miR-182 is an important mediator of GBC metastasis, thus offering a new target for the development of therapeutic agents against GBC.
转化生长因子β（TGF-β）通过调节miRNAs表达在肿瘤转移中发挥重要作用。miR-182是癌症进展调控中的一个重要分子。本研究旨在评估miR-182在TGF-β诱导的癌症转移中的作用。在本研究中，我们发现与正常对照相比，GBC组织中miR-182水平显著上调，并且与未发生转移的原发性肿瘤相比，在随后发生转移的原发性肿瘤中miR-182表达明显增加。TGF-β在GBC细胞中诱导miR-182表达，miR-182的过表达促进GBC细胞迁移和侵袭，而miR-182的抑制则抑制TGF-β诱导的癌细胞迁移和侵袭。用特异性抑制剂阻断miR-182可有效抑制体内肺转移。我们进一步确定细胞黏附分子1（CADM1）是miR-182的一个新靶基因。miR-182在体外和体内均负向调节CADM1表达。重要的是，在GBC细胞中重新表达CADM1可部分消除miR-182诱导的细胞侵袭。
miR-182是GBC转移的重要介质，因此为开发抗GBC治疗药物提供了新靶点。
