横纹肌肉瘤相关差异miRNAs和靶基因的生物信息学分析

Bioinformatics analysis of differential miRNAs and target genes in rhabdomyosarcoma

摘要:

目的： 运用生物信息学分析人正常横纹肌和横纹肌肉瘤（rhabdomyosarcoma，RMS）差异miRNAs和靶基因，为研究RMS提供新思路。方法： GEO2R分析RMS组织的差异miRNAs，利用Sangerbox绘制火山图。TargetScan、miRDB、miRwalk预测靶基因并利用Veen分析交集靶基因。Enrichr分析靶基因的GO富集分析和KEGG信号通路。Cytoscape结合生存分析筛选hub基因及miRNAs与hub基因的分子调控网络。结果： GEO2R分析发现2 549个差异miRNAs，上调和下调miRNAs分别有1 318个和1 231个，根据|log₂FC|>1.5，P<0.05筛选出6个差异miRNAs（上调：miR-410-3p、miR-381-3p、miR-483-3p和miR-376a-3p，下调：miR-29c-3p和miR-145-5p）；TargetScan、miRDB、miRwalk分别预测6个差异miRNAs的靶基因后Veen图取交集的靶基因共计1 262个；GO富集和KEGG信号通路分析靶基因富集于RNA聚合酶Ⅱ的调控、调节干细胞多能性的信号通路、Hippo信号通路等过程；Cytoscape筛选出top10 hub基因后结合生存曲线分析显示FBXL3高表达，SPSB4、VHL、SMAD4、NRAS、KRAS低表达时患者预后较好。结论： 利用生物信息学分析正常横纹肌和横纹肌肉瘤组织的差异miRNAs-靶基因，筛选出miR-145-5p（SPSB4、FBXL3、SMAD4、NRAS）、miR-29c-3p（VHL）、miR-381-3p（KRAS），可为横纹肌肉瘤的研究提供潜在的分子靶点。

Abstract:

Objective: To analyze the differential miRNAs and target genes of normal striated muscle and rhabdomyosarcoma (RMS) tissues by using bioinformatics methods, so as to provide new ideas for RMS study. Methods: GEO2R was used to analyze the differential miRNAs of RMS. Sangerbox was used to draw volcanic maps. TargetScan, miRDB and miRwalk were used to predict the intersection of target genes. Enrichr was used to analyze GO enrichment analysis and KEGG signaling pathway of target genes. Cytoscape combined survival analysis was used to screen the hub gene and its molecular regulatory network with miRNAs. Results: According to GEO2R analysis, 2 549 differential miRNAs were obtained, of which 1 318 and 1 231 miRNAs were up-regulated and down-regulated, respectively. According to|log₂FC|>1.5 and P<0.05, six differential miRNAs (up-regualted: miR-410-3p, miR-381-3p, miR-483-3p and miR-376a-3p; down-regulated: miR-29c-3p and miR-145-5p) were screened. TargetScan, miRDB and miR-walk predicted the target genes of the six differential miRNAs, and a total of 1 262 target genes were obtained from the Veen plot. GO enrichment and KEGG signal pathway analysis of differential miRNAs-target genes revealed that enrichment was in the regulation of RNA polymeraseⅡand regulated the signal pathway of stem cell pluripotency and the Hippo signaling pathway. After cytoscape analysis screening top10 hub genes, it combined with survival curve analysis showed that high expression of FBXL3 and low expression of SPSB4, VHL, SMAD4, NRAS and KRAS had a better prognosis. Conclusion: Utilizing bioinformatics to analyze differential miRNAs-target genes of normal striated muscle and RMS, miR-145-5p (SPSB4, FBXL3, SMAD4, NRAS), miR-29c-3p (VHL) and miR-381-3p (KRAS) are screened, which can provide potential molecular targets for the study of RMS.