title: Hepatitis B virus X protein disrupts the balance of the expression of circadian rhythm genes in hepatocellular carcinoma.
abstract: The human circadian rhythm is controlled by at least eight circadian clock genes and disruption of the circadian rhythm is associated with cancer development. The present study aims to elucidate the association between the expression of circadian clock genes and the development of hepatocellular carcinoma (HCC), and also to reveal whether the hepatitis B virus X protein (HBx) is the major regulator that contributes to the disturbance of circadian clock gene expression. The mRNA levels of circadian clock genes in 30 HCC and the paired peritumoral tissues were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A stable HBx-expressing cell line, Bel-7404-HBx, was established through transfection of HBx plasmids. The mRNA level of circadian clock genes was also detected by RT-qPCR in these cells. Compared with the paired peritumoral tissues, the mRNA levels of thePer1,Per2,Per3andCry2genes in HCC tissue were significantly lower (P<0.05), while no significant difference was observed in the expression levels ofCLOCK,BMAL1,Cry1andcasein kinase 1ɛ(CK1ɛ; P>0.05). Compared with Bel-7404 cells, the mRNA levels of theCLOCK,Per1andPer2genes in Bel-7404-HBx cells were significantly increased, while the mRNA levels of theBMAL1,Per3,Cry1,Cry2andCKIɛgenes were decreased (P<0.05). Thus, the present study identified that disturbance of the expression of circadian clock genes is common in HCC. HBx disrupts the expression of circadian clock genes and may, therefore, induce the development of HCC.
authors.affiliation: Department of General Surgery, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430077, P.R. China.
authors.forename: Sheng-Li
authors.initials: SL
authors.lastname: Yang
authors.affiliation: Department of Hepatobiliary Surgery, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550001, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Hepatobiliary Surgery, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550001, P.R. China.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Jiang
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Shenzhen People's Hospital, Second Clinical Medical College, Jinan University, Shenzhen, Guangdong 518000, P.R. China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Xiefan
authors.initials: X
authors.lastname: Fang
authors.affiliation: Department of General Surgery, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430077, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wu
keywords: circadian clock; hepatitis B virus X protein; hepatocellular carcinoma