辐射诱导lncRNA LOC102606465靶基因的筛选及生物信息学分析

Identification and bioinformatic analysis of target genes of lncRNA LOC102606465 induced by ionizing radiation

目的筛选电离辐射诱导的长链非编码RNA LOC102606465靶基因,探索其潜在生物学功能。方法基因芯片检测LOC102606465下游差异表达基因(differentially expressed genes,DEGs),qRT-PCR对部分DEGs进行验证。对DEGs进行GO和KEGG功能富集分析,构建PPI蛋白互作网络,以筛选显著模块及关键枢纽基因。结果siRNA-447和siRNA-541的LOC102606465表达量显著低于siRNA-NC,差异具有统计学意义(t=29.095、13.751,P<0.01)。siRNA-447,siRNA-541共同变化的DEGs有374个(112个上调,262个下调)。qRT-PCR验证发现DEGs表达变化趋势与基因芯片结果一致。GO富集分析发现,下调DEGs显著富集于"氧化还原酶活性作用集群"(分子功能),"基底层"(细胞组分),"铵离子代谢过程"(生物过程);上调DEGs显著富集于"蛋白磷酸酶抑制剂活性"(分子功能),"SNARE复合体"(细胞组分),"纤维蛋白溶解负调节"(生物过程)。KEGG分析发现,DEGs显著富集在外源物质细胞色素P450代谢通路,背腹轴形成信号通路,溶酶体信号通路,甘油酯代谢通路和P53信号通路。基于STRING数据库构建蛋白互作网络(包括194个节点与268个边缘),筛选出1个显著功能模块和5个关键枢纽基因ACTRT3、CDKN1A、DPYD、TMP4、PRKACB。结论LOC102606465可能是调节电离辐射敏感性潜在的生物标志物,其表达下调在细胞响应辐射过程中发挥重要作用,并有望成为调节辐射敏感性的重要靶标。

Objective To screen the target genes of long non-coding RNA LOC102606465,which was previously identified to be induced by ionizing radiation,in order to examine its potential biological role.Methods The downstream differentially expressed genes(DEGs)of LOC102606465 were detected by microarray and partially verified by qRT-PCR.GO and KEGG enrichment analysis was performed,and PPI protein interaction network was constructed to screen significant modules and hub genes.Results The expression of LOC102606465 targeted by siRNA-447 and siRNA-541 was significantly lower than that of siRNA-NC(t=29.095,13.751,P<0.01).A total of 374 common DEGs were identified(112 up-regulated/262 down-regulated)in both siRNA-447 and siRNA-541.The qRT-PCR was used to validate the expression of DEGs,which was consistent with the microarray result.In GO enrichment analysis,down-regulated DEGs were significantly enriched in"oxidoreductase activity,acting on the CH-CH group of donors,NAD or NADP as acceptor"(molecular function),"basal lamina"(cellular component),"ammonium ion metabolic process"(biological process).Up-regulated DEGs were mainly enriched in"protein phosphatase inhibitor activity"(molecular function),"SNARE complex"(cellular component),"negative regulation of fibrinolysis"(biological process).In addition,the KEGG enrichment analysis revealed that DEGs were significantly enriched in"metabolism of xenobiotics by cytochrome P450","dorso-ventral axis formation","lysosome glycerophospholipid metabolism"and"p53 signaling pathway".Based on the STRING database,the PPI network was constructed(including 194 nodes and 268 edges),and one significant module and five key hub genes ACTRT3,CDKN1A,DPYD,TMP4,and PRKACB were identified.Conclusions LOC102606465 could be a potential biomarker for the regulation of ionizing radiation sensitivity,and the down-regulation of LOC102606465 plays an important role in the response to radiation,which would be an important target for regulating radiation sensitivity.