hsa-miR-429的靶基因预测及功能分析
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摘要
目的通过生物信息学方法预测hsa-miRNA-429的靶基因及其靶基因的可能功能。方法通过miRbase和Clustal在线数据库对miR-429的碱基序列及序列在各物种间的保守性和进化发展进行分析;应用TargetScan和miRDB数据库预测hsa-miR-429的靶基因;将预测得到的两个数据库的靶基因交集用DAVID在线数据库进行组织器官表达程度分析、功能富集分析和信号转导通路富集分析。结果 miR-429在人、大猩猩、鼠等多个物种之间具有高度保守性;人的miR-429与猕猴的hsa-miR-429-3p更为接近。两个靶基因预测软件预测的靶基因取交集后共有252个,在血管、肾组织中表达丰富度较高;涉及转录调控、心脏血管平滑肌细胞发育、心肌细胞增殖等51个生物过程,影响蛋白结合、DNA结合、转录因子结合等17个分子功能,显著富集于癌症通路、肾细胞癌、心肌细胞肾上腺素能信号转导等16个信号通路中。结论 hsa-miR-429的靶基因参与体内多种生物活动,且在癌症及心血管疾病的进展中起着重要作用。
Objective To predict the target genes and potential functions of hsa-miR-429 by bioinformatics softwares. Methods The analysis of the conservation and evolution of miR-429 sequences among species were carried out by miRbase and Clustal online database. Then, the target genes of hsa-miR-429 were predicted using TargetScan and miRDB databases. Target gene intersections of the predicted two databases were analyzed by DAVID online database for functional enrichment analysis and signal transduction pathway enrichment analysis. Results miR-429 is highly conserved among human, gorilla, and murine species; human miR-429 is closer to hsa-miR-429-3 p in macaques. Two target gene prediction software predicted a total of 252 target gene intersections, and the expression of miR-429 target genes was higher in blood vessels and kidney tissues, involved 51 biological processes including transcriptional regulation, cardiac vascular smooth muscle cell development, and cardiomyocyte proliferation, affecting 17 molecular functions such as protein binding,DNA binding, and transcription factor binding, and significantly enriched in cancer pathway, renal cell carcinoma, and cardiomyocyte adrenaline. The predicted target genes of miR-429 paticipated in 16 signal transduction paths. Conclusion The target genes of hsa-miR-429 are involved in various biological activities in vivo and play an important role in the progression of cancer and cardiovascular diseases.
Objective To predict the target genes and potential functions of hsa-miR-429 by bioinformatics softwares. Methods The analysis of the conservation and evolution of miR-429 sequences among species were carried out by miRbase and Clustal online database. Then, the target genes of hsa-miR-429 were predicted using TargetScan and miRDB databases. Target gene intersections of the predicted two databases were analyzed by DAVID online database for functional enrichment analysis and signal transduction pathway enrichment analysis. Results miR-429 is highly conserved among human, gorilla, and murine species; human miR-429 is closer to hsa-miR-429-3 p in macaques. Two target gene prediction software predicted a total of 252 target gene intersections, and the expression of miR-429 target genes was higher in blood vessels and kidney tissues, involved 51 biological processes including transcriptional regulation, cardiac vascular smooth muscle cell development, and cardiomyocyte proliferation, affecting 17 molecular functions such as protein binding,DNA binding, and transcription factor binding, and significantly enriched in cancer pathway, renal cell carcinoma, and cardiomyocyte adrenaline. The predicted target genes of miR-429 paticipated in 16 signal transduction paths. Conclusion The target genes of hsa-miR-429 are involved in various biological activities in vivo and play an important role in the progression of cancer and cardiovascular diseases.
引文
[1]李洪东,朱晓姝,王建新.生物信息学研究进展[J].玉林师范学院学报,2018,39(5):2-6.
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[3]Samanta S,Balasubramanian S,Rajasingh S,et al.MicroRNA:a new therapeutic strategy for cardiovascular diseases[J].Trends Cardiovasc Med,2016,26(5):407-419.
[4]张越,刘雯,易青,等.miR-21抑制剂对细胞增殖和MMP2蛋白表达的影响[J].解剖科学进展,2015,21(6):648-651.
[5]陈志伟,郭琳琳,吴嘉美,等.miR-1271-5p促进大鼠心肌细胞增殖[J].解剖科学进展,2018,24(2):153-155.
[6]Chen CZ.MicroRNAs as oncogenes and tumor suppressors[J].New England Journal of Medicine,2007,302(1):1-12.
[7]关旭敏,杨晓蕾.心血管疾病危险因素对肿瘤的作用[J].心血管病学进展,2017,1(5):616-619.
[8]Xu,H,Jin L,Chen Y,et al.Downregulation of microRNA-429protects cardiomyocytes against hypoxia-induced apoptosis by increasing Notch1 expression[J].Int J Mol Med,2016,37(6):1677-1685.
[9]Wu CL,Ho JY,Hung SH,et al.MiR-429 expression in bladder cancer and its correlation with tumor behavior and clinical outcome[J].Kaohsiung J Med Sci,2018,34(6):335-340.
[10]Machá?kováT,Ml?ochováH,Stanik M,et al.MiR-429 is linked to metastasis a-nd poor prognosis in renalcell carcinoma by affecting epithetlial-mesenchymal transition[J].Tumor Biol,2016,37(11):1-6.
[11]Samantarrai D,Mallick B.MiR-429 inhibits metastasis by targeting KIAA-0101 in soft tissue sarcoma[J].Exp Cell Res,2017,357(1):33-39.
[12]Guo C,Zhao D,Zhang Q,et al.MiR-429 suppresses tumor migration and invasion by targeting CRKL in hepatocellular carcinoma via inhibiting Raf/MEK/ERK pathway and epithelialmesenchymal transition[J].Sci Rep,2018,8(1):2375-2376.
[13]Wang Y,Dong X,Hu B,et al.The effects of Micro-429 on inhibition of cervical cancer cells through targeting ZEB1 and CRKL[J].Biomed Pharmacother,2016,80:311-321.
[1]谢腾,王升,马炯,等.生物信息学在中药资源研究中的应用[J].中国中药杂志,2012,37(24):3684-3690.
[3]Samanta S,Balasubramanian S,Rajasingh S,et al.MicroRNA:a new therapeutic strategy for cardiovascular diseases[J].Trends Cardiovasc Med,2016,26(5):407-419.
[4]张越,刘雯,易青,等.miR-21抑制剂对细胞增殖和MMP2蛋白表达的影响[J].解剖科学进展,2015,21(6):648-651.
[5]陈志伟,郭琳琳,吴嘉美,等.miR-1271-5p促进大鼠心肌细胞增殖[J].解剖科学进展,2018,24(2):153-155.
[6]Chen CZ.MicroRNAs as oncogenes and tumor suppressors[J].New England Journal of Medicine,2007,302(1):1-12.
[7]关旭敏,杨晓蕾.心血管疾病危险因素对肿瘤的作用[J].心血管病学进展,2017,1(5):616-619.
[8]Xu,H,Jin L,Chen Y,et al.Downregulation of microRNA-429protects cardiomyocytes against hypoxia-induced apoptosis by increasing Notch1 expression[J].Int J Mol Med,2016,37(6):1677-1685.
[9]Wu CL,Ho JY,Hung SH,et al.MiR-429 expression in bladder cancer and its correlation with tumor behavior and clinical outcome[J].Kaohsiung J Med Sci,2018,34(6):335-340.
[10]Machá?kováT,Ml?ochováH,Stanik M,et al.MiR-429 is linked to metastasis a-nd poor prognosis in renalcell carcinoma by affecting epithetlial-mesenchymal transition[J].Tumor Biol,2016,37(11):1-6.
[11]Samantarrai D,Mallick B.MiR-429 inhibits metastasis by targeting KIAA-0101 in soft tissue sarcoma[J].Exp Cell Res,2017,357(1):33-39.
[12]Guo C,Zhao D,Zhang Q,et al.MiR-429 suppresses tumor migration and invasion by targeting CRKL in hepatocellular carcinoma via inhibiting Raf/MEK/ERK pathway and epithelialmesenchymal transition[J].Sci Rep,2018,8(1):2375-2376.
[13]Wang Y,Dong X,Hu B,et al.The effects of Micro-429 on inhibition of cervical cancer cells through targeting ZEB1 and CRKL[J].Biomed Pharmacother,2016,80:311-321.