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

Yang SL, Yu C, Jiang JX, Liu LP, Fang X, Wu C - Oncol Lett (2014)

Bottom Line: 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 1ɛ (CK1ɛ; 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 CKIɛ genes were decreased (P<0.05).HBx disrupts the expression of circadian clock genes and may, therefore, induce the development of HCC.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430077, P.R. China.

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 1ɛ (CK1ɛ; 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 CKIɛ 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.

No MeSH data available.


Related in: MedlinePlus

Comparison of circadian gene mRNA expression levels between hepatocellular carcinoma (HCC) tissue (T) and matched peritumoral tissue (N). Box boundaries represent the 25th and 75th percentiles of the observed values; capped bars, the 10th and 90th percentiles; solid line, the median. P-values were calculated by the Wilcoxon test. Per1, Per2, Per3 and Cry2 gene expression levels were higher in the peritumoral tissue than in the HCC tissue. CLOCK, BMAL1, Cry1 and CK1ɛ gene expression levels were similar in the HCC and peritumoral tissue. P<0.05 was considered to indicate a statistically significant difference.
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f1-ol-08-06-2715: Comparison of circadian gene mRNA expression levels between hepatocellular carcinoma (HCC) tissue (T) and matched peritumoral tissue (N). Box boundaries represent the 25th and 75th percentiles of the observed values; capped bars, the 10th and 90th percentiles; solid line, the median. P-values were calculated by the Wilcoxon test. Per1, Per2, Per3 and Cry2 gene expression levels were higher in the peritumoral tissue than in the HCC tissue. CLOCK, BMAL1, Cry1 and CK1ɛ gene expression levels were similar in the HCC and peritumoral tissue. P<0.05 was considered to indicate a statistically significant difference.

Mentions: The mRNA levels of circadian clock genes were first determined in 30 HCC and the paired peritumorous tissues using RT-qPCR. It was found that the mRNA levels of Per1, Per2, Per3 and Cry2 in HCC tissues were markedly decreased in comparison with those in the paired peritumoral tissues, while no significant difference was observed in the mRNA levels of CLOCK, BMAL1, Cry1 and CK1ɛ compared with the peritumoral tissues (Fig. 1). In these cases, the majority (70–90%) of the HCC cancerous tissues exhibited downregulation of the circadian clock gene, whereas the remaining cases were either downregulated in the non-cancerous tissues or were cases in which no differential expression of the circadian clock genes was detected. In particular, Per1 and Per3 downregulation was found in 27 (90%) out of the 30 cases analyzed and only three cases (10%) exhibited Per1 and Per2 upregulation in the HCC tissues. It was also found that the majority of the HCC tissues exhibited downregulation of at least four circadian clock genes. Therefore, it could be inferred that the disturbance of circadian clock gene expression is a common event in HCC and results in the disruption of normal circadian rhythm in cancerous cells.


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

Yang SL, Yu C, Jiang JX, Liu LP, Fang X, Wu C - Oncol Lett (2014)

Comparison of circadian gene mRNA expression levels between hepatocellular carcinoma (HCC) tissue (T) and matched peritumoral tissue (N). Box boundaries represent the 25th and 75th percentiles of the observed values; capped bars, the 10th and 90th percentiles; solid line, the median. P-values were calculated by the Wilcoxon test. Per1, Per2, Per3 and Cry2 gene expression levels were higher in the peritumoral tissue than in the HCC tissue. CLOCK, BMAL1, Cry1 and CK1ɛ gene expression levels were similar in the HCC and peritumoral tissue. P<0.05 was considered to indicate a statistically significant difference.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4214404&req=5

f1-ol-08-06-2715: Comparison of circadian gene mRNA expression levels between hepatocellular carcinoma (HCC) tissue (T) and matched peritumoral tissue (N). Box boundaries represent the 25th and 75th percentiles of the observed values; capped bars, the 10th and 90th percentiles; solid line, the median. P-values were calculated by the Wilcoxon test. Per1, Per2, Per3 and Cry2 gene expression levels were higher in the peritumoral tissue than in the HCC tissue. CLOCK, BMAL1, Cry1 and CK1ɛ gene expression levels were similar in the HCC and peritumoral tissue. P<0.05 was considered to indicate a statistically significant difference.
Mentions: The mRNA levels of circadian clock genes were first determined in 30 HCC and the paired peritumorous tissues using RT-qPCR. It was found that the mRNA levels of Per1, Per2, Per3 and Cry2 in HCC tissues were markedly decreased in comparison with those in the paired peritumoral tissues, while no significant difference was observed in the mRNA levels of CLOCK, BMAL1, Cry1 and CK1ɛ compared with the peritumoral tissues (Fig. 1). In these cases, the majority (70–90%) of the HCC cancerous tissues exhibited downregulation of the circadian clock gene, whereas the remaining cases were either downregulated in the non-cancerous tissues or were cases in which no differential expression of the circadian clock genes was detected. In particular, Per1 and Per3 downregulation was found in 27 (90%) out of the 30 cases analyzed and only three cases (10%) exhibited Per1 and Per2 upregulation in the HCC tissues. It was also found that the majority of the HCC tissues exhibited downregulation of at least four circadian clock genes. Therefore, it could be inferred that the disturbance of circadian clock gene expression is a common event in HCC and results in the disruption of normal circadian rhythm in cancerous cells.

Bottom Line: 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 1ɛ (CK1ɛ; 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 CKIɛ genes were decreased (P<0.05).HBx disrupts the expression of circadian clock genes and may, therefore, induce the development of HCC.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430077, P.R. China.

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 1ɛ (CK1ɛ; 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 CKIɛ 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.

No MeSH data available.


Related in: MedlinePlus