Disturbance of circadian gene expression in hepatocellular carcinoma

Authors

  • Yueh-Min Lin,

    1. Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Institute of Clinical Research, Kaohsiung Medical University, Kaohsiung, Taiwan
    2. Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan
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  • Julia H. Chang,

    1. Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Institute of Clinical Research, Kaohsiung Medical University, Kaohsiung, Taiwan
    2. Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan
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  • Kun-Tu Yeh,

    1. Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Institute of Clinical Research, Kaohsiung Medical University, Kaohsiung, Taiwan
    2. Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan
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  • Ming-Yu Yang,

    1. Department of Biotechnology, Fooyin University, Kaohsiung, Taiwan
    2. Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
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  • Ta-Chih Liu,

    1. Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
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  • Sheng-Fung Lin,

    1. Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
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  • Wei-Wen Su,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
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  • Jan-Gowth Chang

    Corresponding author
    1. Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Institute of Clinical Research, Kaohsiung Medical University, Kaohsiung, Taiwan
    2. Taipei Institute of Pathology, Taipei, Taiwan
    • Department of Laboratory Medicine, Kaohsiung Medical University Hospital, 100, TZYOU 1st Road, Kaohsiung, Taiwan.
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Abstract

Circadian rhythm plays an important role in the regulation of digestive system. The human circadian rhythm is controlled by at least nine circadian genes. The aims of this study are to understand the expression of the circadian genes between hepatocellular carcinoma tissues and nontumor tissues, and to explore the possible mechanism(s) contributing to the difference. We analyzed differential expression of the 9 circadian genes in 46 hepatocellular carcinoma and paired noncancerous tissues by real-time quantitative RT-PCR and immunohistochemical detection. We also tested the possible regulatory mechanism(s) by direct sequencing and methylation PCR analysis. Our results showed that decreased expression levels of PER1, PER2, PER3, CRY2, and TIM in hepatocellular carcinomas were observed. Decreased-expression of these genes was not caused by genetic mutations, but by several factors, such as promoter methylation, overexpression of EZH2 or other factors. The downexpression of more circadian genes may result in disturbance of cell cycle, and it is correlated with the tumor size. Downregulation of circadian genes results in disturbance of circadian rhythm in hepatocellular carcinoma which may disrupt the control of the central pacemaker and benefit selective survival of cancerous cells and promote carcinogenesis. © 2008 Wiley-Liss, Inc.

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