胰腺导管腺癌microRNA表达谱的研究

MicroRNA profiles in pancreatic ductal adenocarcinoma

目的应用microRNA（miRNA）高通量生物芯片筛选胰腺导管腺癌及癌旁组织差异表达的miRNA，分析其相关的靶基因。方法收集9例新鲜的胰腺导管腺癌和3例癌旁组织，运用标记713个miRNA的AgilentmiRNA生物芯片筛选胰腺导管腺癌差异表达的miRNA，应用荧光实时定量PCR方法验证表达上调的miRNA。采用TargetScan5．1和miRandaV5分析软件分析差异表达miRNAs的靶基因。结果miRNA芯片筛选出11个胰腺导管腺癌相关的差异表达的miRNA，其中miR-194：it、miR-192＊、miR-602、miR-194表达上调，miR-139-3p、miR-513a-5p、miR-630、miR-30c-1＊、miR-887、miR-508—5p、miR-516a-5p表达下调。miR．192、miR-194及其同源体的表达在31例胰腺癌组织中得到验证。经软件分析，miR-192靶基因有ZEB2、CXCL-2、EEF1A1、ERCC3，miR-192＊靶基因有DCC、SMAIM、FAS，miR-194靶基因有DACH1、IGSF11、PTPN2、RBBP4，miR-194$靶基因有CIMOLG、CIDEB、FHL1。结论胰腺导管腺癌存在11个表达差异的miRNA，这些miRNA可能与胰腺导管腺癌的发生、发展有关。

Objective To study the differentially expressed microRNA （miRNA） between pancreatic ductal adenocarcinoma （PDAC） and para-cancerous tissues, and determine related target genes. Methods Nine fresh PDAC tumor tissues and 3 adjacent normal pancreatic tissues were collected, then Agilent miRNA microarray with 713 miRNA loci was used to identify the differentially expressed miRNA. Real-time PCR method was applied to verify the up-regulated miRNA. TargetScan 5. l and miRandaV5 software were used to analyze the related target genes. Results miRNA microarray identified 11 PDAC related miRNAs, among them, the expressions of miR-194 ＊, miR-192 ＊, miR-602, miR-194 were up-regulated, while the expressions of miR-139-3p, miR-513a-Sp, miR-630, miR-30c-1 ＊, miR-887, miR-508-Sp, miR-516a-Sp were down-regulated. The expressions of miR-192, miR-194 and their homolog were verified in 31 PDAC tumor tissues. After software analysis, it was found that target genes of miR-192 were ZEB2, CXCL-2, EEF1A1, ERCC3, and target genes of miR-192 ＊ were DCC, SMAIM, FAS, and target genes of miR-194 included DACH1, IGSFll, PTPN2, RBBP4, while target genes of miR-194 ＊ included CIMOLG, CIDEB, FHL1. Conclusions Eleven differentially expressed miRNAs are present in PDC, and they may be involved in the occurrence and development of PDC.