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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.
Hepatology 2013; 57(5):1882-92Hep

Abstract

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.

Authors+Show Affiliations

The Department of Medical Genetics, Second Military Medical University, Shanghai, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23239537

Citation

Huang, Jin-feng, et al. "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." Hepatology (Baltimore, Md.), vol. 57, no. 5, 2013, pp. 1882-92.
Huang JF, Guo YJ, Zhao CX, et al. 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. Hepatology. 2013;57(5):1882-92.
Huang, J. F., Guo, Y. J., Zhao, C. X., Yuan, S. X., Wang, Y., Tang, G. N., ... Sun, S. H. (2013). 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. Hepatology (Baltimore, Md.), 57(5), pp. 1882-92. doi:10.1002/hep.26195.
Huang JF, et al. 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. Hepatology. 2013;57(5):1882-92. PubMed PMID: 23239537.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Huang,Jin-feng, AU - Guo,Ying-jun, AU - Zhao,Chen-xi, AU - Yuan,Sheng-xian, AU - Wang,Yue, AU - Tang,Guan-nan, AU - Zhou,Wei-ping, AU - Sun,Shu-han, PY - 2012/09/25/received PY - 2012/12/01/accepted PY - 2012/12/15/entrez PY - 2012/12/15/pubmed PY - 2013/7/6/medline SP - 1882 EP - 92 JF - Hepatology (Baltimore, Md.) JO - Hepatology VL - 57 IS - 5 N2 - UNLABELLED: 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. SN - 1527-3350 UR - https://www.unboundmedicine.com/medline/citation/23239537/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_ L2 - https://doi.org/10.1002/hep.26195 DB - PRIME DP - Unbound Medicine ER -