miRNA-7/21/107 contribute to HBx-induced hepatocellular carcinoma progression through suppression of maspin
| Autor: | Wen Ling Shih, Wen Shu Chen, Wei Chien Huang, Chia Jui Yen, Yun Ju Chen, Shu Jun Chiu, Pei Hsuan Chien, Li Yun Wang, Mien Chie Hung, Jhen Yu Chen, Ching-Chow Chen, Tzu Tang Wei, Hsiao Lin Pan, Chien Yi Ho |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Hepatitis B virus Carcinoma Hepatocellular Cell Survival Blotting Western Antineoplastic Agents Biology medicine.disease_cause Downregulation and upregulation Cell Line Tumor microRNA medicine metastasis Humans Viral Regulatory and Accessory Proteins Anoikis 3' Untranslated Regions Serpins Regulation of gene expression Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Liver Neoplasms Maspin Hep G2 Cells digestive system diseases hepatocellular carcinoma cell Gene Expression Regulation Neoplastic HBx MicroRNAs HEK293 Cells Oncology Tumor progression Host-Pathogen Interactions Multivariate Analysis Disease Progression Trans-Activators Cancer research Female maspin Carcinogenesis Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.4504 |
| Popis: | Maspin suppresses tumor progression by promoting cell adhesion and apoptosis and by inhibiting cell motility. However, its role in tumorigenesis of hepatocellular carcinoma (HCC) remains unclear. The gene regulation of maspin and its relationship with HCC patient prognosis were investigated in this study. Maspin expression was specifically reduced in HBV-associated patients and correlated with their poor prognosis. Maspin downregulation in HCC cells was induced by HBx to promote their motility and resistance to anoikis and chemotherapy. HBx-dependent induction of microRNA-7, -107, and -21 was further demonstrated to directly target maspin mRNA, leading to its protein downregulation. Higher expressions of these microRNAs also correlated with maspin downregulation in HBV-associated patients, and were associated with their poor overall survival. These data not only provided new insights into the molecular mechanisms of maspin deficiency by HBx, but also indicated that downregulation of maspin by microRNAs confers HBx-mediated aggressiveness and chemoresistance in HCC. |
| Databáze: | OpenAIRE |
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