奶牛microRNA-205靶基因及调控网络的精细预测分析
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摘要
目的预测奶牛microRNA-205(bta-miR-205)候选靶基因,对其进行生物信息学精细分析,构建候选靶基因参与的调控网络。方法应用miRBASE、Targetscan和miRWalk软件预测其候选靶基因,经Gene Ontology、Panther、STRING和DAVID软件进行功能注释、分类统计、蛋白质互作及KEGG通路注释和富集分析,通过Cytoscape软件绘制靶基因可能重点参与的调控网络。结果 miR-205基因成熟区序列高度保守,共筛选出288个bta-miR-205候选靶基因,其参与的主要生物进程是细胞过程、代谢过程和生物调控,主要参与形成细胞器等细胞组分,主要分子功能是结合、催化作用。MAPK3等多个候选靶基因存在基因共表达和蛋白互作关系,参与免疫系统、适应性免疫系统、基因表达(转录)、抗原加工等反应途径显著富集在鞘脂、甲状腺激素、PI3K-Akt等信号通路。结论 bta-miR-205的候选靶基因MAPK3等可能通过参与免疫系统、基因表达(转录)、抗原加工等反应途径及鞘脂、甲状腺激素、PI3K-Akt等信号通路,在奶牛炎症疾病抗性、生殖及发育过程调控中发挥重要作用。
Objective To predict the candidate target genes of cow microRNA-205(bta-miR-205),analyze its bioinformatics and construct a regulatory network which the genes involve in. Methods The candidate target genes were predicted by using miRBASE,Targetscan and miRWalk software,while the functional annotation,taxonomic analysis,protein association analysis,KEGG pathway annotation and enrichment analysis were performed by using Gene Ontology,Panther,STRING and DAVID software,and the regulatory network in which the bta-miR-205 candidate target gene may involve was visualized by using Cytoscape software. Results The mature region sequence of miR-205 gene was highly conserved. A total of 288 candidate target genes of bta-miR-205 were screened,which mainly involved in the cell process,metabolism process and biological regulation as well as formation of main cellular components such as organelle,while the main molecular functions were binding and catalytic activities. Gene coexpression and protein interaction were observed in various candidate target genes including MAPK3,and the genes involved in the immune system,adaptive immune system,gene expression(transcription) and antigen processing pathways,which were significantly enriched in sphingolipid,thyroid hormone,PI3K-Akt and other signaling pathways. Conclusion The candidate target genes of btamiR-205,such as MAPK3,may involve in the immune system,gene expression(transcription),antigen processing and other reactions,which play important roles in the regulations of inflammatory disease resistance and reproductive development in dairy cows through sphingolipids,thyroid hormones,PI3K-Akt and other signaling pathways.
Objective To predict the candidate target genes of cow microRNA-205(bta-miR-205),analyze its bioinformatics and construct a regulatory network which the genes involve in. Methods The candidate target genes were predicted by using miRBASE,Targetscan and miRWalk software,while the functional annotation,taxonomic analysis,protein association analysis,KEGG pathway annotation and enrichment analysis were performed by using Gene Ontology,Panther,STRING and DAVID software,and the regulatory network in which the bta-miR-205 candidate target gene may involve was visualized by using Cytoscape software. Results The mature region sequence of miR-205 gene was highly conserved. A total of 288 candidate target genes of bta-miR-205 were screened,which mainly involved in the cell process,metabolism process and biological regulation as well as formation of main cellular components such as organelle,while the main molecular functions were binding and catalytic activities. Gene coexpression and protein interaction were observed in various candidate target genes including MAPK3,and the genes involved in the immune system,adaptive immune system,gene expression(transcription) and antigen processing pathways,which were significantly enriched in sphingolipid,thyroid hormone,PI3K-Akt and other signaling pathways. Conclusion The candidate target genes of btamiR-205,such as MAPK3,may involve in the immune system,gene expression(transcription),antigen processing and other reactions,which play important roles in the regulations of inflammatory disease resistance and reproductive development in dairy cows through sphingolipids,thyroid hormones,PI3K-Akt and other signaling pathways.
引文
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[2]WANG M,MOISA S,KHAN M J,et al.MicroRNA expression patterns in the bovine mammary gland are affected by stage of lactation[J].J Dairy Sci,2012,95(11):6529-6535.
[3]GALIO L,DROINEAU S,YEBOAH P,et al.MicroRNA in the ovine mammary gland during early pregnancy:spatial and temporal expression of miR-21,miR-205,and miR-200[J].Physiol Genomics,2013,45(4):151-161.
[4]IOANNIDIS J,DONADEU F X.Changes in circulating microRNA levels can be identified as early as day 8 of pregnancy in cattle[J].PLoS One,2017,12(4):0174892.
[5]LIANG G,MALMUTHUGE N,MCFADDEN T B,et al.Potential regulatory role of microRNAs in the development of bovine gastrointestinal tract during early life[J].PLoS One,2014,9(3):92592.
[6]ABD EL NABY W S,HAGOS T H,HOSSAIN M M,et al.Expression analysis of regulatory microRNAs in bovine cumulus oocyte complex and preimplantation embryos[J].Zygote,2013,21(1):31-51.
[7]FARRELL D,SHAUGHNESSY R G,BRITTON L,et al.The identification of circulating miRNA in bovine serum and their potential as novel biomarkers of early Mycobacterium avium subsp paratuberculosis infection[J].PLoS One,2015,10(7):0134310.
[8]LUORENG Z M,WANG X P,MEI C G,et al.Expression profiling of peripheral blood miRNA using RNAseq technology in dairy cows with Escherichia coli-induced mastitis[J].Sci Rep,2018,8(1):12693.
[9]LUORENG Z M,WANG X P,MEI C G,et al.Comparison of microRNA profiles between bovine mammary glands infected with Staphylococcus aureus and Escherichia coli[J].Int J Biol Sci,2018,14(1):87-99.
[10]TIWARI M,GUPTA A,SHARMA A,et al.Role of mitogen activated protein kinase and maturation promoting factor during the achievement of meiotic competency in mammalian oocytes[J].J Cell Biochem,2018,119(1):123-129.
[11]ZHAO Y,ZHANG Y,LI J,et al.MAPK3/1 participates in the activation of primordial follicles through mTORC1-KITLsignaling[J].J Cell Physiol,2018,233(1):226-237.
[12]YANG L,WEI Q,GE J,et al.MAPK3/1 is conducive to luteinizing hormone-mediated C-type natriuretic peptide decrease in bovine granulosa cells[J].J Reprod Dev,2016,62(2):137-142.
[13]CHUNG C K,GE W.Human chorionic gonadotropin(hCG)induces MAPK3/1 phosphorylation in the zebrafish ovarian follicle cells independent of EGF/EGFR pathway[J].Gen Comp Endocrinol,2013,188:251-257.
[14]MCGINNIS L A,LEE H J,ROBINSON D N,et al.MAPK3/1(ERK1/2)and myosin light chain kinase in mammalian eggs affect myosin-II function and regulate the metaphase II state in a calcium-and zinc-dependent manner[J].Biol Reprod,2015,92(6):146.
[15]CHEN H,WANG X,YAN X,et al.LncRNA MALAT1 regulates sepsis-induced cardiac inflammation and dysfunction via interaction with miR-125b and p38 MAPK/NfkappaB[J].Int Immunopharmacol,2018,55:69-76.
[16]MU P W,JIANG P,WANG M M,et al.Oestrogen exerts antiinflammation via p38 MAPK/NF-kappaB cascade in adipocytes[J].Obes Res Clin Pract,2016,10(6):633-641.
[17]GUO Y,BAO Y,MA M,et al.Clinical significance of the correlation between PLCE 1 and PRKCA in esophageal inflammation and esophageal carcinoma[J].Oncotarget,2017,8(20):33285-33299.
[18]ELIAS D,VEVER H,LAENKHOLM A V,et al.Gene expression profiling identifies FYN as an important molecule in tamoxifen resistance and a predictor of early recurrence in patients treated with endocrine therapy[J].Oncogene,2015,34(15):1919-1927.
[19]WU Y,ZHANG L,ZHANG Y,et al.Bioinformatics analysis to screen for critical genes between survived and nonsurvived patients with sepsis[J].Mol Med Rep,2018,18(4):3737-3743.
[20]DHAHBI J,LI X,TRAN T,et al.Circulating blood leukocyte gene expression profiles:effects of the Ames dwarf mutation on pathways related to immunity and inflammation[J].Exp Gerontol,2007,42(8):772-788.