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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 the Bel-7404-HBx and control cells. The expression of CLOCK, Per1 and Per2 mRNA was increased in the Bel-7404-HBx cells compared with the control cells, while the expression of BMAL1, Per3, Cry1, Cry2 and CKIɛ mRNA was decreased in the Bel-7404-HBx cells. *P<0.05 vs. BEL-7404-EGFP.
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f3-ol-08-06-2715: Comparison of circadian gene mRNA expression levels between the Bel-7404-HBx and control cells. The expression of CLOCK, Per1 and Per2 mRNA was increased in the Bel-7404-HBx cells compared with the control cells, while the expression of BMAL1, Per3, Cry1, Cry2 and CKIɛ mRNA was decreased in the Bel-7404-HBx cells. *P<0.05 vs. BEL-7404-EGFP.

Mentions: HBx is a multifunctional protein that plays a vital role in the development and progression of HCC. To identify the influence of HBx on the expression of circadian genes, a stable HBx-transfected Bel-7404 cell line was established, termed Bel-7404-HBx cells. Subsequently, HBx mRNA and protein expression was identified in the HBx-transfected cells. As shown in Fig. 2A, HBx mRNA was highly expressed in the Bel-7404-HBx cells, with no HBx mRNA detected in the control cells. In addition, western blot analysis detected the 17-kDa HBx protein in the lysates of the Bel-7404-HBx cells (Fig. 2B). Therefore, HBx was successfully transfected and expressed in the Bel-7404-HBx cells. The expression of circadian clock genes in these cells was assessed. Compared with the control cells, the expression of CLOCK, Per1 and Per2 mRNA was significantly increased in the Bel-7404-HBx cells, while the expression of BMAL1, Per3, Cry1, Cry2 and CKIɛ mRNA was significantly decreased (Fig. 3; P<0.05). Therefore, HBx may disturb circadian clock gene expression in HCC 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 the Bel-7404-HBx and control cells. The expression of CLOCK, Per1 and Per2 mRNA was increased in the Bel-7404-HBx cells compared with the control cells, while the expression of BMAL1, Per3, Cry1, Cry2 and CKIɛ mRNA was decreased in the Bel-7404-HBx cells. *P<0.05 vs. BEL-7404-EGFP.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3-ol-08-06-2715: Comparison of circadian gene mRNA expression levels between the Bel-7404-HBx and control cells. The expression of CLOCK, Per1 and Per2 mRNA was increased in the Bel-7404-HBx cells compared with the control cells, while the expression of BMAL1, Per3, Cry1, Cry2 and CKIɛ mRNA was decreased in the Bel-7404-HBx cells. *P<0.05 vs. BEL-7404-EGFP.
Mentions: HBx is a multifunctional protein that plays a vital role in the development and progression of HCC. To identify the influence of HBx on the expression of circadian genes, a stable HBx-transfected Bel-7404 cell line was established, termed Bel-7404-HBx cells. Subsequently, HBx mRNA and protein expression was identified in the HBx-transfected cells. As shown in Fig. 2A, HBx mRNA was highly expressed in the Bel-7404-HBx cells, with no HBx mRNA detected in the control cells. In addition, western blot analysis detected the 17-kDa HBx protein in the lysates of the Bel-7404-HBx cells (Fig. 2B). Therefore, HBx was successfully transfected and expressed in the Bel-7404-HBx cells. The expression of circadian clock genes in these cells was assessed. Compared with the control cells, the expression of CLOCK, Per1 and Per2 mRNA was significantly increased in the Bel-7404-HBx cells, while the expression of BMAL1, Per3, Cry1, Cry2 and CKIɛ mRNA was significantly decreased (Fig. 3; P<0.05). Therefore, HBx may disturb circadian clock gene expression in HCC 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