國家衛生研究院 NHRI:Item 3990099045/7939
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    題名: Dysregulation of the TGFBI gene is involved in the oncogenic activity of the nonsense mutation of hepatitis B virus surface gene sW182*
    作者: Jiang, SS;Huang, SF;Huang, MS;Chen, YT;Jhong, HJ;Chang, IC;Chen, YT;Chang, JW;Chen, WL;Lee, WC;Chen, MF;Yeh, CT;Matsuura, I
    貢獻者: National Institute of Cancer Research;Institute of Molecular and Genomic Medicine
    摘要: The nonsense mutations of the hepatitis B virus (HBV) surface (S) gene have been reported to have oncogenic potential. We have previously identified several transforming nonsense mutations of the HBV S gene from hepatocarcinoma (HCC) patients. Among them, the sW182* mutant (the stop codon for W182) showed the most potent oncogenicity in a mouse xenograft model using stably transfected NIH3T3 cells. This study is aimed at understanding the molecular mechanisms leading to the oncogenic activity of the sW182* mutant. A gene expression microarray in combination with gene set enrichment analysis (GSEA) revealed differentially expressed gene sets in the sW182* cells, including those related to cell-cycle regulation, DNA repair, and genome instability. Of the differentially expressed genes, the transforming growth factor-β-induced (TGFBI) gene was further validated to be dysregulated in sW182* cells. This dysregulation was accompanied by hypermethylation of the TGFBI promoter. The level of cyclin D1, a negatively regulated TGFBI target, was highly elevated in the sW182* mutant cells, which is consistent with the potent oncogenicity. Furthermore, frequent abnormal mitosis and multinucleation were observed in the mutant cells. Exogenous expression of TGFBI alleviated the oncogenic activity of sW182*. In human HBV-related HCC cancerous tissue, expression of TGFBI was downregulated in 25 of the 55 (45%) patients examined, suggesting that TGFBI dysregulation could occur in HBV-related HCC development in some cases. These results suggest that dysregulation of TGFBI is involved in the oncogenic activity of the sW182* mutant of the hepatitis B virus S gene.
    日期: 2014-07
    關聯: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 2014 Jul;1842(7):1080-1087.
    Link to: http://dx.doi.org/10.1016/j.bbadis.2014.03.007
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0925-4439&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000336698400020
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84898795185
    顯示於類別:[江士昇] 期刊論文
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    [黃秀芬] 期刊論文

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