Hepatitis B virus X protein induced hypermethylation of RUNX3 through DNMT3A in HCC cells
LIN Wan-song1, LIN Jie2, LIN Qiao-yan1, ZHOU Zhi-feng1, LI Jie-yu1, YE Yun-bin1
1. Tumor Immunology Laboratory of Fujian Provincial Cancer Hospital,Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou 350014, China; 2. Pathology Department, Fujian Provincial Hospital, the Shengli Clinical Medical Collegeof Fujian Medical University, Fuzhou 350001, China
Abstract:We investigated the effect of hepatitis B virus X protein (HBx) on runt-related transcription factor 3 (RUNX3) in hepatocellular carcinoma (HCC). The expression of RUNX3 was detected by quantitative real-time PCR and western blot as well as the methylation of RUNX3 promoter CpG island was evaluated by methylation specific PCR in HCC cells transfected with HBx recombinant plasmids. The small interfering RNA (siRNA) targeting DNA methyltransferase 3A (DNMT3A) were co-transfected with HBx recombinant plasmids into HCC cells, and then the expression of RUNX3 was measured. In addition, the expression and methylation of RUNX3 were analyzed in 21 HCC tissues. Result showed that ectopic HBx inhibited the expression of RUNX3 and induced hypermethylation of RUNX3 CpG island in HCC cells. Furthermore, this inhibitory effect was abrogated by DNMT3A siRNA. The transcription of RUNX3 was higher in HCC tissues with HBx negative than tissues with HBx positive. But the methylation of RUNX3 CpG island exhibited the opposite trend. Our data indicate that HBx may downregulate the expression of RUNX3 through epigenetic mechanism.
林万松, 林洁, 林巧燕, 周智锋, 李洁羽, 叶韵斌. 乙型肝炎病毒X蛋白通过DNMT3A诱导肝癌细胞RUNX3基因高甲基化[J]. 中国人兽共患病学报, 2016, 32(8): 717-722.
LIN Wan-song, LIN Jie, LIN Qiao-yan, ZHOU Zhi-feng, LI Jie-yu, YE Yun-bin. Hepatitis B virus X protein induced hypermethylation of RUNX3 through DNMT3A in HCC cells. Chinese Journal of Zoonoses, 2016, 32(8): 717-722.
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