Hepatitis B virus X protein (HBx)-related long noncoding RNA (lncRNA) down-regulated expression by HBx (Dreh) inhibits hepatocellular carcinoma metastasis by targeting the intermediate filament protein vimentin
| Autor: | Yingjun Guo, Shuhan Sun, Weiping Zhou, Jinfeng Huang, Chen-xi Zhao, Sheng-xian Yuan, Guan-nan Tang, Yue Wang |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Carcinoma Hepatocellular Molecular Sequence Data Down-Regulation Mice Transgenic Vimentin In Vitro Techniques medicine.disease_cause Mice Cell Movement Gene expression medicine Animals Humans Viral Regulatory and Accessory Proteins Neoplasm Metastasis Cell Proliferation Regulation of gene expression Mice Inbred BALB C Base Sequence Hepatology biology Oncogene Liver Neoplasms Middle Aged Hepatitis B digestive system diseases Long non-coding RNA Gene Expression Regulation Neoplastic Survival Rate Disease Models Animal HBx Real-time polymerase chain reaction Trans-Activators Cancer research biology.protein Female RNA Long Noncoding Carcinogenesis |
| Zdroj: | Hepatology. 57:1882-1892 |
| ISSN: | 0270-9139 |
| DOI: | 10.1002/hep.26195 |
| Popis: | The hepatitis B virus X protein (HBx) has been implicated as an oncogene in both epigenetic modifications and genetic regulation during hepatocarcinogenesis, but the underlying mechanisms are not entirely clear. Long noncoding RNAs (lncRNAs), which regulate gene expression with little or no protein-coding capacity, are involved in diverse biological processes and in carcinogenesis. We asked whether HBx could promote hepatocellular carcinoma (HCC) by regulating the expression of lncRNAs. In this study we investigated the alteration in expression of lncRNAs induced by HBx using microarrays and real-time quantitative polymerase chain reaction (PCR). Our results indicate that HBx transgenic mice have a specific profile of liver lncRNAs compared with wildtype mice. We identified an lncRNA, down-regulated expression by HBx (termed lncRNA-Dreh), which can inhibit HCC growth and metastasis in vitro and in vivo, act as a tumor suppressor in the development of hepatitis B virus (HBV)-HCC. LncRNA-Dreh could combine with the intermediate filament protein vimentin and repress its expression, and thus further change the normal cytoskeleton structure to inhibit tumor metastasis. We also identified a human ortholog RNA of Dreh (hDREH) and found that its expression level was frequently down-regulated in HBV-related HCC tissues in comparison with the adjacent noncancerous hepatic tissues, and its decrement significantly correlated with poor survival of HCC patients. Conclusion: These findings support a role of lncRNA-Dreh in tumor suppression and survival prediction in HCC patients. This discovery contributes to a better understanding of the importance of the deregulated lncRNAs by HBx in HCC and provides a rationale for the potential development of lncRNA-based targeted approaches for the treatment of HBV-related HCC. (HEPATOLOGY 2013) |
| Databáze: | OpenAIRE |
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