|
- 现金
- 62111 元
- 精华
- 26
- 帖子
- 30441
- 注册时间
- 2009-10-5
- 最后登录
- 2022-12-28
|
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†‡§
Jin-feng Huang1,¶,
Ying-jun Guo1,§,
Chen-xi Zhao1,
Sheng-xian Yuan2,
Yue Wang1,
Guan-nan Tang1,
Wei-ping Zhou2,
Shu-han Sun1,‖,*
Article first published online: 22 APR 2013
DOI: 10.1002/hep.26195
Copyright © 2012 American Association for the Study of Liver Diseases
Hepatology
Volume 57, Issue 5, pages 1882–1892, May 2013
1
The Department of Medical Genetics, Second Military Medical University, Shanghai, China
2
The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
§
*These authors contributed equally to this work.
¶
These authors contributed equally to this work.
‖
fax: +86-21-81871053
Email: Shu-han Sun ([email protected])
*Department of Medical Genetics, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, P.R. China
†
Potential conflict of interest: Nothing to report.
‡
This work was supported in part by grants from the National Natural Science Foundation of China (No. 81071700, 81171936, 81071680 and 31171251).
§
*These authors contributed equally to this work.
¶
These authors contributed equally to this work.
‖
fax: +86-21-81871053
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. (HEPATOLOGY 2013)
|
|
发表于 2013-5-14 20:27
