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学科主题: 基础医学
题名:
An integrated analysis of SOCS1 down-regulation in HBV infection-related hepatocellular carcinoma
作者: Zhang, X.1,2; Wang, J.1,2; Cheng, J.1,2; Ding, S.1,2; Li, M.1,2; Sun, S.3,5; Zhang, L.4; Liu, S.; Chen, X.1,2; Zhuang, H.1,2; Lu, F.1,2
关键词: p53 ; hepatitis B virus ; suppressor of cytokine signalling 1 ; methylation ; hepatocellular carcinoma
刊名: JOURNAL OF VIRAL HEPATITIS
发表日期: 2014-04-01
DOI: 10.1111/jvh.12137
卷: 21, 期:4, 页:264-271
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Gastroenterology & Hepatology ; Infectious Diseases ; Virology
研究领域[WOS]: Gastroenterology & Hepatology ; Infectious Diseases ; Virology
关键词[WOS]: NATURAL MENOPAUSE ; CANCER ; GENE ; METHYLATION ; HYPERMETHYLATION ; GROWTH ; P53 ; INHIBITION ; SENESCENCE ; SUPPRESSOR
英文摘要:

Persistent inflammation together with genetic/epigenetic aberrations is strongly associated with chronic Hepatitis B virus (HBV) infection-related hepatocarcinogenesis. Here, we investigated the alterations of the suppressor of cytokine signalling (SOCS) family genes in HBV-related hepatocellular carcinoma (HCC). A total of 116 patients with HCC were enrolled in this study. The methylation statuses of SOCS1-7 and CISH genes were quantitatively measured and clinicopathological significance of SOCS1 methylation was statistically analysed. The gene copy number variation was assayed by aCGH. Luciferase reporter assay and Western blot were used to detect the involvement of SOCS1 in p53 signalling. We found high frequencies of SOCS1 gene hypermethylation in both tumour (56.03%) and adjacent nontumour tissues (54.31%), but tumour tissues exhibited increased methylation intensity (24.01% vs 13.11%, P<0.0001), particularly in patients with larger tumour size or cirrhosis background (P<0.0001). In addition, the frequency and intensity of SOCS1 hypermethylation in tumour tissues were both significantly higher than those in nontumour tissues in male gender patients and in patients >= 45years old (P=0.0214 and P<0.0001, P=0.0232 and P<0.0001, respectively). SOCS1 gene deletion was found in 8 of 25 aCGH assayed tumour specimens, which was associated with lower SOCS1 mRNA expression (P=0.0448). Furthermore, ectopic SOCS1 overexpression could activate the p53 signalling pathway in HCC cell lines. Hypermethylation of SOCS2-7 and CISH genes was seldom found in HCC. Our results suggested that the gene loss and epigenetic silencing of SOCS1 were strongly associated with HBV-related HCC.

语种: 英语
所属项目编号: Z111107067311027 ; 2012ZX10002005 ; B07001
项目资助者: Project of Beijing Municipal Science and Technology Commission ; National S & ; T Major Project for Infectious Diseases ; Leading Academic Discipline Project of Beijing ; 111 Project
WOS记录号: WOS:000332237800005
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57855
Appears in Collections:基础医学院_病原生物学系_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Microbiol, Beijing 100191, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Ctr Infect Dis, Sch Basic Med Sci, Beijing 100191, Peoples R China
3.Harbin Med Univ Daqing, Coll Pharm, Daqing, Peoples R China
4.Henan Tumor Hosp, Dept Hepatopancreatobiliary Surg, Zhengzhou, Peoples R China
5.Capital Med Univ, Beijing Youan Hosp, Beijing Artificial Liver Treatment Training Ctr, Beijing, Peoples R China

Recommended Citation:
Zhang, X.,Wang, J.,Cheng, J.,et al. An integrated analysis of SOCS1 down-regulation in HBV infection-related hepatocellular carcinoma[J]. JOURNAL OF VIRAL HEPATITIS,2014,21(4):264-271.
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