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Hepatitis B virus X protein upregulates expression of SMYD3 and C-MYC in HepG2 cells

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Abstract

The carcinogenic role of Hepatitis B X (HBX) in hepatocellular carcinoma (HCC) remains largely unknown. Histone H3 lysine 4 methyltransferase SMYD3 was found to be over-expressed and have a pro-carcinogenic effect in HCC. The role of HBX in regulating SMYD3 activity and the corresponding C-MYC gene in HCC carcinogenesis was investigated. SMYD3 and C-MYC expression in HBV-negative HepG2 and HBV-positive HepG2.2.15 were detected by real time PCR and Western blot. After transfection of HBX into HepG2, SMYD3 and C-MYC protein expression was detected and the apoptosis and proliferation of hepatoma cells were assayed. After SMYD3 expression in HepG2 with HBX transfection downregulated by siRNA, the corresponding C-MYC expression, cellular apoptosis, and proliferation were assayed by FACS. SMYD3 mRNA and protein and C-MYC protein were significantly higher in HepG2.2.15 than in HepG2. HBX transfection resulted in enhanced SMYD3 and C-MYC expressions, decreased cell apoptosis, and increased cell proliferation in HepG2 cells. Knocking down of SMYD3 in HepG2 with HBX transfection inhibited C-MYC expression and promoted apoptosis. These results suggest that HBX upregulates SMYD3 expression in HepG2, which may promote hepatoma development and progress. C-MYC may act as a down-stream gene in HBX-SMYD3-related hepatocarcinogenesis.

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Acknowledgement

The paper was supported by Natural Science Foundation of China (NSF) No. 30672067 and 30700190.

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Authors and Affiliations

  1. Hepatobiliary Center, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Jiefang Dadao 1277, Wuhan, 430022, People’s Republic of China

    Lian Yang, Jun He, Libo Chen & Guobin Wang

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  1. Lian Yang
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  2. Jun He
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  3. Libo Chen
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Correspondence to Libo Chen.

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Yang, L., He, J., Chen, L. et al. Hepatitis B virus X protein upregulates expression of SMYD3 and C-MYC in HepG2 cells. Med Oncol 26, 445–451 (2009). https://doi.org/10.1007/s12032-008-9144-1

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  • DOI: https://doi.org/10.1007/s12032-008-9144-1

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