Methylation-associated silencing of microRNA-129-3p promotes epithelial-mesenchymal transition, invasion and metastasis of hepatocelluar cancer by targeting Aurora-A
| Autor: | Lei Lu, Longbang Chen, Jing Chen, Rui Wang, Kai Zhang, Shi-Yun Cui, Yan Pan, Chen Li, Bing Feng, Ziman Zhu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Pathology medicine.medical_specialty Carcinoma Hepatocellular Epithelial-Mesenchymal Transition MAP Kinase Signaling System Down-Regulation Mice Nude Aurora-A Metastasis 03 medical and health sciences Mice Phosphatidylinositol 3-Kinases 0302 clinical medicine Downregulation and upregulation Cell Line Tumor microRNA medicine Gene silencing metastasis Animals Humans Neoplasm Invasiveness Epithelial–mesenchymal transition Neoplasm Metastasis Protein kinase B PI3K/AKT/mTOR pathway Aurora Kinase A Mice Inbred BALB C business.industry Liver Neoplasms hepatocelluar cancer Cancer Hep G2 Cells DNA Methylation medicine.disease Prognosis digestive system diseases miR-129-3p MicroRNAs 030104 developmental biology HEK293 Cells Oncology 030220 oncology & carcinogenesis Cancer research Female business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Shiyun Cui 1, * , Kai Zhang 1, * , Chen Li 1 , Jing Chen 1 , Yan Pan 1 , Bing Feng 1 , Lei Lu 2 , Ziman Zhu 3 , Rui Wang 1 , Longbang Chen 1 1 Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, Jiangsu, PR China 2 Liver Disease Center of PLA, The 81th Hospital of PLA, Nanjing 210002, Jiangsu, PR China 3 Department of Hepatobiliary Surgery, First Hospital Affiliated to the Chinese PLA General Hospital, Haidian District, Beijing 100048, PR China * These authors have contributed equally to this work Correspondence to: Rui Wang, email: wangrui218@163.com Longbang Chen, email: chenlongbang@yeah.net Keywords: hepatocelluar cancer, miR-129-3p, Aurora-A, epithelial-mesenchymal transition, metastasis Received: July 26, 2016 Accepted: October 14, 2016 Published: October 25, 2016 ABSTRACT Metastasis and recurrence has become one major obstacle for further improving the survival of hepatocelluar cancer (HCC) patients. Therefore, it is critical to elucidate the mechanisms involved in HCC metastasis. This study aimed to investigate the roles of microRNA (miR)-129-3p in HCC metastasis and its possible molecular mechanisms. By using microarray analysis to compare levels of different miRNAs in HCC tissues with or without lymph node metastasis (LNM), we showed that HCC tissues with LNM had reduced levels of miR-129-3p, which was related to its promoter hypermethylation and correlated with tumor metastasis, recurrence and poor prognosis. Gain - and loss - of - function assays indicated that re-expression of miR-129-3p could reverse epithelial-mesenchymal transition (EMT), and reduce in vitro invasion and in vivo metastasis of HCC cells. Aurora-A, a serine/threonine protein kinase, was identified as a direct target of miR-129-3p. Knockdown of Aurora-A phenocopied the effect of miR-129-3p overexpression on HCC metastasis. In addition, Aurora-A upregulation could partially rescue the effect of miR-129-3p. We further demonstrated that activation of PI3K/Akt and p38-MAPK signalings were involved in miR-129-3p-mediated HCC metastasis. These findings suggest that methylation-mediated miR-129-3p downregulation promotes EMT, in vitro invasion and in vivo metastasis of HCC cells via activation of PI3K/Akt and p38-MAPK signalings partially by targeting Aurora-A. Therefore, miR-129-3p may be a novel prognostic biomarker and potential therapeutic target for HCC. |
| Databáze: | OpenAIRE |
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