Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 461, Issue 4, Pages 618-623Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2015.04.075
Keywords
miR-129-5p; ETS1; Hepatocellular carcinoma; Invasion
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Funding
- National Natural Science Foundation of China [81071871, 81101862, 81472253, 81472258, 81172079, 81072047, 81201930]
- Natural Science Foundation of Guangdong Province [S2013010016831, 2014A030313063]
- Science and Technology Planning Project of Guangdong Province [2011B060300012]
- Foundation for Youth Teacher by Sun Yat-Sen University [11ykpy16]
- Key Project of Guangzhou Municipal Science & Technology Planning [2011J4100053]
- Doctoral Research Foundation of Guangzhou Medical University [2010C23]
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MiR-129-5p is deregulated in various human cancers and has been associated with hepatocellular carcinoma (HCC) progression. However, the underlying mechanisms of miR-129-5p involvement in the development and progression of HCC and the effects of miR-129-5p deregulation on the clinical characteristics observed in HCC patients remain poorly understood. We therefore investigated the correlation between low miR-129-5p expression and vascular invasion, intrahepatic metastasis, and poor patient survival. Ectopic restoration of miR-129-5p expression in HCC cells suppressed cellular migration and invasion and the expression of v-ets erythroblastosis virus E26 oncogene homolog 1 (ETS1), while inhibition of endogenous miR-129-5p caused an increase in these parameters. We identified the ETS1 gene as a novel direct target of miR-129-5p. SiRNA-mediated ETS1 knockdown rescued the effects of anti-miR-129-5p inhibitor in HCC cell lines, while the effects of miR-129-5p overexpression were partially phenocopied in the knockdown model. In addition, miR-129-5p levels inversely correlated with those of ETS1 in HCC cells and tissues. Taken together, our findings indicate an important role for miR-129-5p in the molecular etiology of invasive HCC and suggest that miR-129-5p could have potential therapeutic applications in HCC. (C) 2015 Elsevier Inc. All rights reserved.
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