MicroRNA-379-5p inhibits tumor invasion and metastasis by targeting FAK/AKT signaling in hepatocellular carcinoma
| Autor: | Ju-Tao Feng, Jiong-Qiang Huang, Xiao-Hui Huang, Shi-Hao Dong, Jian-cong Sun, Wei Yi, Jing-Song Chen, Hua-Shu Li, Gao-fang Zhan, Zhi-Jie Huang |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty Carcinoma Hepatocellular Epithelial-Mesenchymal Transition Mice Nude Biology Metastasis Focal adhesion 03 medical and health sciences 0302 clinical medicine RNA interference Cell Movement Internal medicine Cell Line Tumor microRNA medicine Animals Humans Neoplasm Invasiveness Epithelial–mesenchymal transition neoplasms Protein kinase B 3' Untranslated Regions Gene knockdown Mice Inbred BALB C Binding Sites Base Sequence Liver Neoplasms Cell migration medicine.disease digestive system diseases Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology 030220 oncology & carcinogenesis Focal Adhesion Kinase 1 Cancer research RNA Interference Proto-Oncogene Proteins c-akt Neoplasm Transplantation |
| Zdroj: | Cancer letters. 375(1) |
| ISSN: | 1872-7980 |
| Popis: | Some microRNAs (miRNAs) have been implicated in hepatocellular carcinoma (HCC) development and progression. However, the roles and mechanisms of several miRNAs in HCC remain poorly understood. Here, we report that miR-379-5p, which is down-regulated in HCC tissues and cell lines, is associated with advanced TNM stage and metastasis in HCC. The ectopic overexpression of miR-379-5p inhibited HCC cell migration, invasion, epithelial-to-mesenchymal transition (EMT) and metastasis both in vitro and in vivo. Conversely, miR-379 knockdown increased migration, invasion and EMT in HCC cells. Moreover, miR-379-5p exerted this function by directly targeting focal adhesion kinase (FAK) 3'-UTR and repressing FAK expression, thus leading to suppression of AKT signaling. Furthermore, the tumor suppressive effects of miR-379-5p in HCC cells were reversed by activating AKT signaling or restoring FAK expression. In clinical samples of HCC, miR-379-5p negatively correlated with FAK, which was up-regulated in HCC. Taken together, our findings highlight the important role of miR-379-5p in regulating the EMT and metastasis of HCC by targeting FAK/AKT signaling, suggesting that miR-379-5p may represent a novel potential therapeutic target and prognostic marker for HCC. |
| Databáze: | OpenAIRE |
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