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

Nov 1, 2014Oncology letters

Hepatitis B virus protein alters daily rhythm gene activity in liver cancer

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Abstract

The mRNA levels of circadian clock genes were significantly lower in hepatocellular carcinoma (HCC) tissue compared to paired peritumoral tissues.

Disruption of circadian clock gene expression is commonly observed in HCC.
The hepatitis B virus X protein (HBx) may disrupt circadian clock gene expression.
In HCC tissues, specific circadian clock genes showed significantly decreased expression.
In HBx-expressing cells, certain circadian clock genes had increased mRNA levels, while others decreased.

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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,,andgenes in HCC tissue were significantly lower (P<0.05), while no significant difference was observed in the expression levels of,,and(; P>0.05). Compared with Bel-7404 cells, the mRNA levels of the,andgenes in Bel-7404-HBx cells were significantly increased, while the mRNA levels of the,,,andgenes 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. Per1Per2Per3Cry2CLOCK BMAL1Cry1casein kinase 1ɛ CK1ɛ CLOCK Per1Per2BMAL1Per3Cry1Cry2CKIɛ

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

Abstract

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