Title: MicroRNA-30a increases tight junction protein expression to suppress the epithelial-mesenchymal transition and metastasis by targeting Slug in breast cancer
Authors: Chang, Chia-Wei
Yu, Jyh-Cherng
Hsieh, Yi-Hsien
Yao, Chung-Chin
Chao, Jui-I
Chen, Po-Ming
Hsieh, Hsiao-Yen
Hsiung, Chia-Ni
Chu, Hou-Wei
Shen, Chen-Yang
Cheng, Chun-Wen
生物科技學系
Department of Biological Science and Technology
Keywords: breast cancer metastasis;EMT;miR-30a;slug;claudin
Issue Date: 29-Mar-2016
Abstract: The epithelial-to-mesenchymal (EMT) transition is a prerequisite for conferring metastatic potential during tumor progression. microRNA-30a (miR-30a) expression was significantly lower in aggressive breast cancer cell lines compared with non-invasive breast cancer and non-malignant mammary epithelial cell lines. In contrast, miR-30a overexpression reversed the mesenchymal appearance of cancer cells to result in a cobblestone-like epithelial phenotype. We identified Slug, one of the master regulators of EMT, as a target of miR-30a using in silico prediction. Reporter assays indicated that miR-30a could bind to the 3\'-untranslted region of Slug mRNA. Furthermore, we linked miR-30a to increased expression of claudins, a family of tight junction transmembrane proteins. An interaction between Slug and E-box in the claudin promoter sequences was reduced upon miR-30a overexpression, further leading to reduction of filopodia formation and decreased invasiveness/metastasis capabilities of breast cancer cells. Consistently, delivery of miR-30a in xenografted mice decreased tumor invasion and migration. In patients with breast cancer, a significantly elevated risk of the miR-30a(low)/CLDN2(low)/FSCNhigh genotype was observed, linking to a phenotypic manifestation of larger tumor size, lymph node metastasis, and advanced tumor stage among patients. In conclusion, the miR-30a/Slug axis inhibits mesenchymal tumor development by interfering with metastatic cancer cell programming and may be a potential target for therapy in breast cancer.
URI: http://hdl.handle.net/11536/133820
ISSN: 1949-2553
Journal: ONCOTARGET
Volume: 7
Issue: 13
Begin Page: 16462
End Page: 16478
Appears in Collections:Articles