期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1863, 期 7, 页码 1601-1611出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamcr.2016.04.016
关键词
miR-181b-3p; EMT; Metastasis; YWHAG; Snail
资金
- Korea Institute of Radiological and Medical Sciences (KIRAMS)
- Ministry of Science, ICT and Future Planning, Republic of Korea [1711021781/741602, 1711021925/743402]
- Ministry of Science, ICT & Future Planning, Republic of Korea [505152016] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Epithelial-mesenchymal transition (EMT) is essential for increased invasion and metastasis during cancer progression. Among the candidate EMT-regulating microRNAs that we previously identified, miR-181b-3p was found to induce EMT in MCF7 breast cancer cells, as indicated by an EMT-characteristic morphological change, increased invasiveness, and altered expression of an EMT marker. Transfection with a miR-181b-3p inhibitor reduced the expression of mesenchymal markers and the migration and invasion of highly invasive breast cancer cells. miR-181b-3p induced the upregulation of Snail, a master EMT inducer and transcriptional repressor of E-cadherin, through protein stabilization. YWHAG was identified as a direct target of miR-181b-3p, downregulation of which induced Snail stabilization and EMT phenotypes. Ectopic expression of YWHAG abrogated the effect of miR-181b-3p, including Snail stabilization and the promotion of invasion. In situ hybridization and immunohistochemical analyses indicated that YWHAG expression was inversely correlated with the expression of miR-181b-3p and Snail in human breast cancer tissues. Furthermore, transfection with miR-181b-3p increased the frequency of metastatic nodule formation in the lungs of mice in experimental metastasis assays using MDA-MB-231 cells. Taken together, our data suggest that miR-181b-3p functions as a metastasis activator by promoting Snail-induced EMT, and may therefore be a therapeutic target in metastatic cancers. (C) 2016 Elsevier B.V. All rights reserved.
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