DNMT3B基因异常表达与肝癌发生的相关性研究

Study on relationship between abnormal expression of DNA-methyltransferase 3B and hepatocellular carcinogenesis

目的探讨DNMT3B和肝癌发生的关系。方法用实时荧光定量RT-PCR方法分析正常肝细胞系、肝癌癌旁细胞系及肝癌癌细胞系中DNMT1、DNMT3A、DNMT3B的表达谱,以及DNMT3B表达抑制后在肝癌细胞系SMMC-7721中出现表达上调的与肿瘤发生相关的基因PDCD4和MBD3的表达。结果DNMT1,DNMT3A,DNMT3B在肝癌细胞系中存在高表达的趋势,表达水平一致性的明显高于肝癌癌旁和正常肝细胞系,提示这些酶与肝癌的发生相关。结论DNMT3B表达抑制后肝癌细胞系SMMC-7721中与肝癌发生相关的MBD3和PDCD4基因表达水平上调,表明DNMT3B沉默后,诱导了下游肿瘤抑制基因的过表达,推测DNMT3B在肝癌发生中通过某种机制调控下游肿瘤抑制基因的表达。

Objective To explore the relationship between DNA-methyltransferase 3 B （DNMT3 B） gene and hepatocellular carcinogenesis. Methods Using real-time fluorescent quantitative RT-PCR to analyze the expressions of DNMT1, DNMT3A and DNMT3B in normal liver cell line, pericacinoma cell line and hepatocellular carcinoma cell line respectively. Real-time fluorescent quantitative RT-PCR was also used to confirm the up-regulation of some genes related to tumorgenesis, such as PDCD4 and MBD3 detected by cDNA mi roarray for DNMT3B RNAi of hepatocellular carcinoma cell line SMMC-7721. Results There was over-expression of DNMTs in hepatocellular carcinoma cell line compared to that in pericacinoma cell line and normal liver cell line, especially the expression of DNMT3B was significantly increased. Conclusion These obtained data indicated that DNMT3B may be involved in hepatocellular carcinogenesis and the regulation for the expression of some tumor suppressor genes related to carcinogenesis by certain mechanism.