hsa-miR-21-5p靶基因预测及其在急性肾损伤中的调控机制

Prediction of hsa-miR-21-5p Targeted Genes and It's Regulation Mechanisms in Acute Kidney Injury

目的:对hsa-miR-21-5p进行靶基因预测及生物信息学分析,为验证hsa-miR-21-5p靶基因及进一步研究hsa-miR-21-5p在急性肾损伤(AKI)中的调控作用提供数据支持。方法:应用Pubmed、Google等检索工具,以miR-21和AKI为关键词,检索miR-21与AKI相关的所有文献;应用miRBase获取各物种miR-21-5p序列,分析保守性;利用miRecord数据库进行靶基因预测,选取PicTar、PITA、RNAhybrid和TargetScan预测靶基因交集和DIANA LAB-TarBase 6.0已有实验数据支持的hsa-miR-21-5p靶基因作为研究的基因集合,进行功能注释、功能富集性分析(GO-analysis)及信号转导通路富集性分析。结果:miR-21水平在AKI肾脏、血及尿中均升高。miR-21-5p在多物种间具有序列保守性。hsa-miR-21-5p预测靶基因富集于生长发育、物质代谢与合成、细胞运动、细胞周期、增殖、凋亡、分化等生物学过程及蛋白连接、转录因子活性、转移酶活性、染色质结合、核苷酸结合、核苷结合、核酸结合、转录激活活性、连接酶活性等分子功能上,存在于胞内细胞器、细胞器界膜、细胞器组分、蛋白复合体、非膜性细胞器、细胞器管腔、极性生长位点等细胞组分中。预测靶基因富集于P53、TGF-β、细胞周期、MAPK、腺癌、膀胱癌、癌症通路、小细胞肺癌、慢性粒细胞白血病、黑色素瘤、前列腺癌、脑胶质瘤、大肠癌、非小细胞肺癌、子宫内膜癌、肌萎缩性侧索硬化症共16条通路中。结论:(1)miR-21水平在AKI肾脏、血及尿中均升高,对AKI有保护作用;(2)miR-21-5p在多物种间具有高度保守性;(3)hsa-miR-21-5p参与了多种生理、病理过程;(4)hsa-miR-21-5p对多条通路具有调控作用,可能通过调节细胞凋亡、炎症反应等参与AKI病理生理过程。

Objective： Bioinformatics software and database were applied to predict the targeted genes of hsa-miR-21-5p,so as to indentify the targeted genes and provide theory guide to further study of hsa-miR-21-5p＇s regulation mechanism in acute kidney injury（ AKI）.Methods： All literatures of miR-21 and acute kidney injury were searched in Pubmed and Google,et al. miRBase was used to obtain the mature sequences of miR-21 in all species and to analyze the conservation. miRecord database was applied to predict the targeted genes of hsa-miR-21-5p. Choosing intersection of software of PicTar,PITA,RNAhybrid and TargetScan and available experimental data supporting hsa-miR-21-5p targeted genes in DIANA LAB-TarBase 6. 0 as collection of genes,which were further done functional annotation,functional enrichment analysis（ GO-analysis） and the signal transduction pathway enrichment analysis. Results： The level of miR-21 was increased in kidney,blood and urine. Bioinformatics software and database analysis found miR-21-5p was conserved in many species. hsa-miR-21-5p predicted target genes enriched in biological processes such as growth,metabolism,biosynthesis,cell motility,cell cycle,proliferation,apoptosis,differentiation,and in molecules function such as protein linked,transcription factor activity,transferase activity,chromatin binding,nucleotide binding,nucleotide binding,nucleic acid binding,transcriptional activation activity,ligase activity,lipid binding and nucleoside triphosphatase activity. The target genes presented in organelles,membrane of organelle,organelle fraction,protein complexes,non-membranous organelles,organelle lumen,polarity and other cell growth locus component. hsa-miR-21-5p predicted targeted genes enriched in sixteen pathways such as the P53,TGF-β,cell cycle,MAPK,adenocarcinoma,bladder cancer,cancer pathways,small cell lung cancer,chronic myelogenous leukemia,melanoma,prostate cancer,glioma,colorectal cancer,non-small cell lung cancer,endometrial cancer and amyotrophic lateral sclerosis. Conclusions：（ 1） The level of miR-21 in AKI kidney tissue,blood and urine are increased,and has a protective effect with AKI;（ 2） miR-21-5p is highly conserved in species;（ 3） hsa-miR-21-5p is involved in many physiological and pathological processes;（ 4） hsa-miR-21-5p has regulatory role in multiple signaling pathways and disease pathways,possibly through regulation of targeted genes which regulate apoptosis,inflammation in acute kidney injury pathology physiological processes.