hsa-miR-145-5p在胰腺癌中的表达及生物信息学分析

Expression of hsa-miR-145-5p in pancreatic cancer and its bioinformatics analysis

目的研究hsa-miR-145-5p在胰腺癌患者及正常人血浆中的表达模式,探究hsa-miR-145-5p作为胰腺癌诊断标记物的可行性。进一步阐明其在胰腺癌的发生发展过程中可能的调控机制。方法采用生物信息学方法进行hsa-miR-145-5p的靶基因预测及功能分析,选择miRanda、TargetScan和RNAhybrid三种软件预测hsa-miR-145-5p的靶基因并结合现有数据库筛选有实验数据支持的靶基因,进一步进行GO功能富集分析,KEGG Pathway富集分析和蛋白互作分析,研究靶基因功能。qPCR验证胰腺癌患者及正常对照组血浆中hsa-miR-145-5p表达。结果hsa-miR-145-5p序列在各物种间高度保守;预测其靶基因共得到8 679个,且有实验数据支持靶基因有1 408个;有实验数据支持的靶基因GO富集分析主要显著富集于胞内运输、基因表达调控、细胞内信号传导、细胞生长调控、能量代谢等生物学过程和功能上(FDR<0.01)。KEGG Pathway富集分析靶基因显著富集于p53信号通路、ErbB信号通路、MAPK信号通路、慢性骨髓白血病、膀胱癌、胶质瘤、前列腺癌、胰腺癌等(P<0.01),表明hsa-miR-145-5p在胰腺癌中有重要的调控作用。相较于正常组,患病组hsa-miR-145-5p表达下调。结论 hsa-miR-145-5p调控多个肿瘤发生相关的基因,在胰腺癌发生相关的生物学过程中具有重要的调控功能,为胰腺癌miRNA标记物的研究提供了线索。

Objective To investigate the expression pattern of hsa-miR-145-Sp in the plasma of patients in pancreatic cancer and normal person, and explore the feasibility of hsa-miR-145-Sp as a diagnostic marker for pancreatic cancer, and further clarify its possible regulatory mechanism in the development and progression of pancreatic cancer. Methods Tar- get genes prediction and functional analysis of hsa-miR-145-Sp by bioinformatics method. MiRanda,TargetScan and RNA- hybrid software were used to predict the target genes of hsa-miR-145-Sp and the target genes supported by experimental data, and GO enrichment, KEGG Pathway enrichment analysis and protein interaction analysis were performed to study the function of target genes. RT-qPCR was used to detect the expression of hsa-miR-145-Sp in pancreatic cancer and normal control group. Results hsa-miR-145-Sp mature sequences were high conserved in several species. The number of target genes were predicted to be 8 679, and the number of target genes that the experimental data supported was 1 408. The GO enrichment analysis of the target genes, which was supported by the experimental data, was mainly concentrated in the bio- logical processes and functions such as intracellular transport, gene expression regulation, intracellular signal transduction, cell growth regulation, energy metabolism, and so on（ FDR 〈 0.01 ）. KEGG pathway enrichment analysis was significantly enriched in p53 signaling pathway, ErbB signaling pathway, MAPK signaling pathway, chronic myeloid leukemia, bladder cancer, glioma, prostate cancer, pancreatic cancer, and so on （ P 〈 0.01 ）. Compared with the normal group, the expression of hsa-miR-ldS-Sp was down regulated. Conclusion hsa-miR-145-Sp regulates multiple tumor related genes, plays an important regulatory role in the biological process of pancreatic cancer and provides clues for the study of a miRNA diag- nostic marker in pancreatic cancer.