MicroRNA 122对肝癌细胞基因表达谱的影响

Effects of MicroRNA 122 on Gene Expression Profiles of Hepatocellular Carcinoma Cells

为研究microRNA(miR-122)对肝癌细胞Hep3B基因表达谱的影响,并探讨其在肝癌发生过程中的可能作用,构建了miR-122稳定高表达的Hep3B细胞,利用基因表达谱芯片技术筛选得到和对照组细胞比较的差异表达基因.研究结果显示,2倍以上变化的差异表达基因有490个,其中上调的有345个,下调的有145个.这些基因中有16个与肿瘤发生相关,其它基因涉及细胞周期、信号转导、细胞凋亡和细胞增殖分化等众多生物学过程.这些结果提示,miR-122可能在肝癌发生的过程中发挥作用,并可能与这些差异表达基因密切相关.另外,还结合生物信息学方法,在下调表达的基因中预测了miR-122可能直接作用的靶基因.本研究初步探讨了miR-122在肝癌细胞中的生物学功能,为进一步研究miR-122在肝癌发生中的作用奠定了基础,同时也为miRNA的生物学功能及其作用机制的研究提供了一些参考.

MicroRNAs （miRNAs） are a class of endogenous small, non-coding RNAs that negatively regulate target mRNA expressions at the post-transcriptional level, miRNAs have been linked to many significant physiological processes. Misregulation of microRNA function might contribute to human diseases. In cancer researches, it has been shown that miRNAs can act as oncogenes or tumor suppressors. MicroRNA 122 （miR-122） is specifically expressed and highly abundant in the liver. It is down-regulated in hepatocellular carcinoma （HCC） and HCC cell lines, and could be a biomarker for HCC. To reveal the role of miR-122 in hepatocarcinogenesis process, a cell line that could stably express miR-122 was screened in Hep3B cells. In combination with gene expression profiling microarray, the results revealed the effects of miR-122 on gene expression profiles of Hep3B cells. We found that 490 genes were differentially expressed with a 2-fold change. Among them, 345 genes were up-regulated and 145 genes were down-regulated. Further analysis showed that 16 genes were involved in carcinogenesis; the others were linked to many significant biological processes, such as cell cycle, cell proliferation and differentiation, signal transduction, apoptosis, etc. These results indicated that miR-122 played some kind of roles in hepatocarcinogenesis process and its function might be related to these differentially expressed genes. In addition, we predicted the target genes by bioinformatics method in the down-regulated genes. Further investigations are needed to verify their functions. These findings establish a foundation for further researching the functions and acting mechanisms of miR-122 in HCC. The study initially investigated the biological functions of miR-122 in HCC cells, and provides a clue for researching the biological functions of miRNAs.