组蛋白去乙酰化酶抑制剂TSA对食管癌细胞ncRNA/mRNA表达谱的影响

Analysis of differential ncRNA and mRNA expression profiles in esophageal cancer cell treated with histone deacetylase inhibitor TSA

目的:分析组蛋白去乙酰化酶抑制剂TSA处理前后,食管癌细胞株EC109中差异表达的非编码RNA(ncRNA)和mRNA表达谱,初步预测与TSA作用相关的ncRNA和mRNA。方法:采用MTT、细胞周期等方法检测TSA的效应;运用应用芯片技术分别检测TSA处理前后EC109细胞中ncRNA和mRNA表达谱变化,并对差异ncRNA和mRNA表达谱进行整合分析。结果:TSA以剂量时间依赖方式抑制细胞增殖,细胞周期阻滞和凋亡的发生。芯片检测共发现461个ncRNA和758个mRNA显著性差异表达,生物信息学分析显示差异涉及红比霉素、阿霉素代谢过程、氧化还原、核小体的装配、染色质结构组织和端粒的结构组织等。通过数据库分析预测及整合分析,得到了361个ncRNA-mRNA靶基因对。结论:差异表达的ncRNA和mRNA对TSA的生物学效应密切关联,为进一步研究基因功能及其在肿瘤中的生物学意义奠定基础。

Objective:To identify differentially expressed non-coding RNA(ncRNA)and mRNA in esophageal cancer cells,and explore their roles in esophageal cancer.Methods:Human esophageal cancer cell EC109 was treated with TSA,and RNA was isolated for chip analysis.Chip technology was used to detect the expressions of ncRNA and mRNA in these samples.The profiles of differentially expressed ncRNA and mRNA were integrated and analyzed.The target genes of differentially expressed genes were confirmed,and biological molecular function annotation system was used to confirm biological function of these genes.Results:Treatment of TSA significantly induced cell growth retardation and cell apoptosis.Result of chip analysis showed 461 ncRNA and 758 mRNA were differentially expressed after TSA treatment.The target genes were correlated with multifunction including daunorubicin and oxidant-reduction process,chromatin organization and nucleosome assembly.361 coding-lncRNA pairs were predicted by co-expression analysis.Conclusion:The differential expressed ncRNA and target genes in EC109 cells after TSA treatment were correlated with the biological activity of TSA,which contributed to further analysis of the gene functions and its biological significance in cancer cells.