Identification of cellular genes showing differential expression associated with hepatitis B virus infection

作     者：Yasuo Fukuhara Takeshi Suda Makoto Kobayashi Yasushi Tamura Masato Igarashi Nobuo Waguri Hirokazu Kawai Yutaka Aoyagi 

作者机构：Division of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University 1-757 Asahimachi-dori Chuo-ku Niigata Niigata 951-8122 Japan 

出 版 物：《World Journal of Hepatology》 (世界肝病学杂志（英文版）（电子版）)

年 卷 期：2012年第4卷第4期

页      面：139-148页

学科分类：1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 100401[医学-流行病与卫生统计学] 10[医学] 

基　　金：Japan Society for the Promotion of Science  JSPS  (23659395) 

主　　题：Hepatitis B virus Differential gene expression Hepatocellular carcinoma Gene expression signature Adipose most abundant 2 

摘      要：AIM: To investigate the impact of hepatitis B virus (HBV) infection on cellular gene expression, by conducting both in vitro and in vivo studies. METHODS: Knockdown of HBV was targeted by stable expression of short hairpin RNA (shRNA) in huH-1 cells. Cellular gene expression was compared using a human 30K cDNA microarray in the cells and quantified by real-time reverse transcription-polymerase chain reaction (RT-PCR) (qRT-PCR) in the cells, hepatocellular carcinoma (HCC) and surrounding non-cancerous liver tissues (SL). RESULTS: The expressions of HBsAg and HBx protein were markedly suppressed in the cells and in HBx transgenic mouse liver, respectively, after introduction of shRNA. Of the 30K genes studied, 135 and 103 genes were identified as being down- and up-regulated, respectively, by at least twofold in the knockdown cells. Functional annotation revealed that 85 and 62 genes were classified into four up-regulated and five down-regulated functional categories, respectively. When gene expression levels were compared between HCC and SL, eight candidate genes that were confirmed to be up- or down-regulated in the knockdown cells by both microarray and qRT-PCR analyses were not expressed as expected from HBV reduction in HCC, but had similar expression patterns in HBV- and hepatitis C virus-associated cases. In contrast, among the eight genes, only APM2 was constantly repressed in HBV non-associated tissues irrespective of HCC or SL. CONCLUSION: The signature of cellular gene expression should provide new information regarding the pathophysiological mechanisms of persistent hepatitis and hepatocarcinogenesis that are associated with HBV infection.