miR-381-5p靶向ERCC4调节乳腺癌细胞顺铂耐药的生物信息学分析

Bioinformatics analysis of mir-381-5p targeting ERCC4 to regulate cisplatin resistance in breast cancer cells

目的利用生物信息学方法分析miR-381-5p序列,预测其靶基因,寻找miR-381-5p在人野生乳腺癌细胞(MDA-MB-231)耐受顺铂过程中所调控的相关基因,为后续的深入研究提供理论依据。方法应用RNAhybrid2.1.2、Miranda3.3a、TargetScan7.03种在线工具预测miR-381-5p靶基因,取其交集靶基因;对交集靶基因进行Gene Ontology(GO)分子功能、生物学过程分析;根据分析结果,筛选出与miR-381-5p有关的显著差异表达基因。结果应用3种在线软件预测获得52个交集靶基因;GO分子功能集中于蛋白质N端结合、转录因子结合、双链DNA结合等(P<0.01);生物学过程集中于同型半胱氨酸代谢过程、细胞生物合成过程的调控、核染色体隔离等(P<0.01);miR-381-5p可负调控LHPP、HOXC5、LBX2、ERCC4、CREB3L3、IPCEF1、CD151、RAB43、TCF21与MTHFD1这10个靶基因,ERCC4表达差异最为显著。结论分析结果初步提示miR-381-5p可能通过调控ERCC4的表达来参与乳腺癌耐顺铂过程,为后续的实验性研究与治疗策略提供了线索。

Objective:To analyze the sequence of mir-381-5p by bioinformatics,predict its target genes,and search for the related genes regulated by mir-381-5p in the cisplatin resistance of human wild breast cancer cells(mda-mb-231),to finally provide theoretical basis for further research.Methods:Three kinds of online tools,namely RNAhybrid2.1.2,miranda3.3a and TargetScan7.0,were applied to predict the target genes of mir-381-5p,and their hybrid target genes were obtained.The molecular functions and biological processes of intersection target genes were analyzed.According to the analysis results,significant differentially expressed genes related to mir-381-5p were screened out.Results:Three kinds of online software were used to predict 52 intersection target genes.GO molecular functions focus on protein n-terminal binding,transcription factor binding,double-stranded DNA binding,etc.(P<0.01).The biological processes focused on homocysteine metabolism,regulation of cell biosynthesis and nuclear chromosome isolation(P<0.01).Mir-381-5p negatively regulated 10 target genes,namely LHPP,HOXC5,LBX2,ERCC4,CREB3L3,IPCEF1,CD151,RAB43,TCF21 and MTHFD1,and ERCC4 expression showed the most significant difference.Conclusion:The analysis results preliminarily suggest that mir-381-5p may be involved in cisplatin resistance of breast cancer by regulating the expression of ERCC4,which provides clues for subsequent experimental studies and treatment strategies.