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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-145-5p in the plasma of patients with pancreatic cancer and normal human and explore the feasibility of hsa-miR-145-5p as a diagnostic marker of pancreatic cancer. Further clarify its possible regulatory mechanism in the occurrence and development of pancreatic cancer. Methods The bioinformatics method was used to predict and analyze the target gene of hsa-miR-145-5p. The target genes of hsa-miR-145-5p were predicted by using miRanda, TargetScan and RNAhybrid software, and combined with the existing database screening experiments Data support the target gene, further GO function enrichment analysis, KEGG Pathway enrichment analysis and protein interaction analysis, research target gene function. qPCR to verify the expression of hsa-miR-145-5p in plasma of patients with pancreatic cancer and normal control group. Results The sequence of hsa-miR-145-5p was highly conserved among all species. A total of 8 679 target genes were predicted and there were 1 408 target genes supported by experimental data. GO enrichment analysis of target genes supported by experimental data Significantly enriched in intracellular transport, gene expression and regulation, intracellular signaling, cell growth regulation, energy metabolism and other biological processes and functions (FDR <0.01). The target gene of 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 and pancreatic cancer (P <0.01), indicating that hsa-miR -145-5p plays an important regulatory role in pancreatic cancer. Compared with the normal group, the expression of hsa-miR-145-5p in the diseased group was down-regulated. Conclusion hsa-miR-145-5p regulates multiple tumor-related genes and plays an important regulatory role in the biological processes involved in pancreatic carcinogenesis. It provides a clue for the study of miRNA markers in pancreatic cancer.