MiR-497 suppresses angiogenesis and metastasis of hepatocellular carcinoma by inhibiting VEGFA and AEG-1
| Autor: | Pei-Yuan Li, Ying Chang, Ju-Sheng Lin, Kun-peng Ke, Yu-Nan Zhang, Jingjun Yan, Xing-Xing He, Min Wang, Jiazhi Liao |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Vascular Endothelial Growth Factor A Pathology medicine.medical_specialty Carcinoma Hepatocellular Angiogenesis Blotting Western Mice Nude Apoptosis Cell Line Metastasis Nude mouse Downregulation and upregulation Cell Movement Cell Line Tumor microRNA medicine cancer Animals Humans Neoplasm Metastasis 3' Untranslated Regions Cell Proliferation tumor biology Mice Inbred BALB C Neovascularization Pathologic biology Reverse Transcriptase Polymerase Chain Reaction business.industry Liver Neoplasms Membrane Proteins RNA-Binding Proteins Cancer hepatocellular carcinoma Hep G2 Cells medicine.disease biology.organism_classification Xenograft Model Antitumor Assays Gene Expression Regulation Neoplastic MicroRNAs Vascular endothelial growth factor A Oncology Hepatocellular carcinoma Female business Cell Adhesion Molecules Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.5012 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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