miR-19b promotes breast cancer metastasis through targeting MYLIP and its related cell adhesion molecules
Metrics: PDF 1738 views | HTML 2675 views | ?
Luqing Zhao1,4, Yuelong Zhao3, Yanong He3 and Yitao Mao2
1Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
2Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
3School of Computer Science and Engineering, South China University of Technology, Guangzhou, Guangdong 510640, China
4Department of Pathology, School of Basic Medical Science, Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China
Yitao Mao, email: [email protected]
Keywords: miR-19b, MYLIP, cell adhesion molecules, breast cancer, metastasis
Received: February 03, 2017 Accepted: June 19, 2017 Published: July 17, 2017
miR-19b is a key molecule for cancer development, however its crucial roles in breast cancer metastasis are rarely studied right now. In this study, using several bioinformatics databases to predict the downstream targets for miR-19b, we verified that a novel target gene, myosin regulatory light chain interacting protein (MYLIP), could be directly down-regulated by miR-19b through its 3'-UTR region. MYLIP belongs to the cytoskeletal protein clusters and is involved in the regulation of cell movement and migration. We further explored that miR-19b was highly expressed and negatively correlated with MYLIP expression in breast cancer patient samples from the TCGA database. And the over-expression of miR-19b or inhibition of MYLIP facilitated the migration and metastasis of breast cancer cells, through conducting the wound healing assay and transwell invasion assay. Additionally, miR-19b could obviously promote breast tumor growth in mouse models and affect the expressions of cell adhesion molecules (including E-Cadherin, ICAM-1 and Integrin β1) by down-regulating E-Cadherin expression and up-regulating ICAM-1 and Integrin β1 expressions in vitro and in vivo. Meanwhile, miR-19b effectively activated the Integrin β downstream signaling pathways (such as the Ras-MAPK pathway and the PI3K-AKT pathway) and elevated the expression levels of essential genes in these two pathways. Taken together, these findings comprehensively illustrate the regulatory mechanisms ofmiR-19b in breast cancer metastasis, and provide us new insights for exploring MYLIP and its related cell adhesion molecules as promising therapeutic targets to interfere breast cancer development.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.