Analysis of gene expression during glucocorticoid-induced apoptosis of rat primary thymocytes

Glucocorticoids induce rapid apoptosis of rat primary thymocytes through mechanisms requiring altered gene expression. The determination of genes regulating glucocorticoid-induced apoptosis of lymphocytes has received considerable attention. However, the role of specific non-coding microRNAs in the regulation of glucocorticoid-induced apoptosis of lymphocytes is poorly defined. Using deep sequencing analysis, we have identified microRNAs differentially expressed during glucocorticoid-induced apoptosis of rat primary thymocytes. We have also identified numerous loci that harbor probable novel microRNAs. Furthermore, we have validated the glucocorticoid-responsive expression of 2 novel microRNAs in the apoptotic rat primary thymocyte. These 2 novel microRNAs are predicted to target numerous messenger RNAs throughout the genome. Using whole genome expression analysis, we now seek to correlate the altered expression of these novel microRNAs with the expression of their predicted target mRNAs during glucocorticoid-induced apoptosis.糖皮质激素可通过依赖基因表达改变的分子机制，诱导大鼠原代胸腺细胞发生快速细胞凋亡。阐明调控淋巴细胞糖皮质激素诱导细胞凋亡的基因，一直是学界关注的重要课题。然而，特定非编码微小RNA（microRNA）在淋巴细胞糖皮质激素诱导细胞凋亡调控中的作用，目前仍未得到明确阐释。本研究通过深度测序分析，鉴定出大鼠原代胸腺细胞在糖皮质激素诱导细胞凋亡过程中差异表达的microRNA；同时还发现了多个可能包含新型microRNA的基因座。此外，本研究已在发生凋亡的大鼠原代胸腺细胞中，验证了2种新型microRNA的糖皮质激素应答表达模式。预测这2种新型microRNA可靶向调控基因组内的大量信使RNA（messenger RNA）。本研究拟通过全基因组表达分析，将这些新型microRNA的表达变化与其预测靶标mRNA在糖皮质激素诱导细胞凋亡过程中的表达水平进行关联分析。