1. MiR-497 suppresses angiogenesis and metastasis of hepatocellular carcinoma by inhibiting VEGFA and AEG-1.
- Author
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Yan JJ, Zhang YN, Liao JZ, Ke KP, Chang Y, Li PY, Wang M, Lin JS, and He XX
- Subjects
- 3' Untranslated Regions genetics, Adult, Animals, Apoptosis genetics, Blotting, Western, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular pathology, Cell Adhesion Molecules metabolism, Cell Line, Cell Line, Tumor, Cell Movement genetics, Cell Proliferation genetics, Female, Gene Expression Regulation, Neoplastic, Hep G2 Cells, Humans, Liver Neoplasms metabolism, Liver Neoplasms pathology, Male, Membrane Proteins, Mice, Inbred BALB C, Mice, Nude, Neoplasm Metastasis, Neovascularization, Pathologic metabolism, RNA-Binding Proteins, Reverse Transcriptase Polymerase Chain Reaction, Vascular Endothelial Growth Factor A metabolism, Xenograft Model Antitumor Assays, Carcinoma, Hepatocellular genetics, Cell Adhesion Molecules genetics, Liver Neoplasms genetics, MicroRNAs genetics, Neovascularization, Pathologic genetics, Vascular Endothelial Growth Factor A genetics
- Abstract
Hepatocellular carcinoma (HCC) is a worldwide malignance and displays marked vascular abnormalities and active metastasis. MicroRNAs (miRNAs) have been shown to play important roles in regulating tumor properties in cancer, however, whether miR-497 contributes to HCC angiogenesis or metastasis remains unclear. In this study, we found that miR-497 was significantly down-regulated in HCC tissue samples and cell lines. Gain-of-function and loss-of-function studies revealed that miR-497 could repress both the pro-angiogenic and metastatic ability of HCC cells. Subsequent investigations disclosed that miR-497 directly inhibited the 3'-untranslated regions (UTRs) of vascular endothelial growth factor A (VEGFA) and astrocyte elevated gene-1 (AEG-1). Furthermore, overexpression of these targets antagonized the function of miR-497. Based on nude mouse models, we demonstrated that overexpression of miR-497 significantly repressed microvessel densities in xenograft tumors and reduced pulmonary metastasis. In conclusion, our findings indicate that miR-497 downregulation contributes to angiogenesis and metastasis in HCC.
- Published
- 2015
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