Hepatitis B virus X protein disrupts the balance of the expression of circadian rhythm genes in hepatocellular carcinoma

Yang,Sheng‑Li; Yu,Chao; Jiang,Jian‑Xin; Liu,Li‑Ping; Fang,Xiefan; Wu,Chao

doi:10.3892/ol.2014.2570

Hepatitis B virus X protein disrupts the balance of the expression of circadian rhythm genes in hepatocellular carcinoma

Authors:
- Sheng‑Li Yang
- Chao Yu
- Jian‑Xin Jiang
- Li‑Ping Liu
- Xiefan Fang
- Chao Wu
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Affiliations: Department of General Surgery, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430077, P.R. China, Department of Hepatobiliary Surgery, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550001, P.R. China, Department of Hepatobiliary and Pancreatic Surgery, Shenzhen People's Hospital, Second Clinical Medical College, Jinan University, Shenzhen, Guangdong 518000, P.R. China, Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL 32610, USA
Published online on: September 26, 2014 https://doi.org/10.3892/ol.2014.2570
Pages: 2715-2720

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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 the Per1, Per2, Per3 and Cry2 genes in HCC tissue were significantly lower (P<0.05), while no significant difference was observed in the expression levels of CLOCK, BMAL1, Cry1 and casein kinase 1ε (CK1ε; P>0.05). Compared with Bel‑7404 cells, the mRNA levels of the CLOCK, Per1 and Per2 genes in Bel‑7404‑HBx cells were significantly increased, while the mRNA levels of the BMAL1, Per3, Cry1, Cry2 and CKIε genes 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.

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