Hepatitis B virus X protein upregulates expression of SMYD3 and C-MYC in HepG2 cells.
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.
Yang
Lian
L
Hepatobiliary Center, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Jiefang Dadao 1277, Wuhan 430022, People's Republic of China.
He
Jun
J
Chen
Libo
L
Wang
Guobin
G
D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D005434:Flow Cytometry; D056945:Hep G2 Cells / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000502:physiology*; D015854:Up-Regulation; D054334:Viral Regulatory and Accessory Proteins
C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D011495:Histone-Lysine N-Methyltransferase; C506278:SMYD3 protein, human