微RNA18与B细胞易位基因2在肝癌细胞中差异表达相关性的研究

The relationship between microRNA-18 and BTG2 in the carcinogenesis of hepatocellular carcinoma

目的研究微RNA18（miR18）对肝癌细胞HepG2基因表达谱的影响，预测其靶基因，初步探讨miR-18与抗增殖基因B细胞易位基因2（BTG2）两者在肝癌发生过程中差异表达的相关性。方法利用基因表达谱芯片技术筛选HepG2的微RNA差异表达谱，应用生物信息学方法预测表达明显上调的miR-18的靶基因，初步筛选出直接调控的靶基因为抗增殖基因BTG2；应用RT-PCR和Northernblot法分析BTG2正常与肝癌组织中的表达情况。结果生物信息学分析结果显示miR-18分子调控的下游靶基因有609个，涉及细胞增殖、分化和凋亡、转录调节等众多生理和病理过程；抗增殖基因BTG2在肝癌组织和细胞中呈明显低表达。结论miR-18在肝癌细胞中表达明显上调，并可能负性调控抗增殖基因BTG2在肝癌细胞中的表达，两者共同在肝癌细胞增殖方面发挥着重要作用。

Objective To study the difference ofmicroRNA expression between HepG2 cells and L02 ceils, and to identify the target genes ofmicroRNA-18 （miR-18）. Methods The differentially expressed miRNAs between HepG2 cells and L02 cells were identified by miRNA chip. Target genes ofmiR-18 were predicted bioinformatically. Furthermore, the expression of B-cell translocation gene 2 （BTG2）, a putative target gene of miR-18, was analyzed in hepatocellular carcinoma tissues and the surrounding non-cancerous tissues by RT-PCR and northern blot. Results miR- 18 was over-expressed in HepG2 cells compared to L02 cells. Altogether 609 genes, including genes involved in cell proliferation, differentiation, apoptosis and tran- scriptional regulation, are identified as putative miR-18 targets. The mRNA level of BTG2 was much lower in hepatocellular carcinoma tissues than in the corresponding non-cancerous tissues. Conclusion miR-18 is over-expressed in HepG2 cells compared to L02 cells, and it may negatively regulate the expression of BTG2, a tumor suppressor gene.