Sui Weiguo, Shi Zhoufang, Xue Wen, Ou Minglin, Zhu Ying, Chen Jiejing, Lin Hua, Liu Fuhua, Dai Yong
Nephrology Department of Guilin No. 181 Hospital, Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi 541004, P.R. China.
College of Life Science of Guangxi Normal University, Guilin, Guangxi 541004, P.R. China.
Oncol Rep. 2017 Mar;37(3):1804-1814. doi: 10.3892/or.2017.5415. Epub 2017 Feb 1.
The aim of the present study was to screen gastric cancer (GC) tissue and adjacent tissue for differences in mRNA and circular (circRNA) expression, to analyze the differences in circRNA and mRNA expression, and to investigate the circRNA expression in gastric carcinoma and its mechanism. circRNA and mRNA differential expression profiles generated using Agilent microarray technology were analyzed in the GC tissues and adjacent tissues. qRT-PCR was used to verify the differential expression of circRNAs and mRNAs according to the interactions between circRNAs and miRNAs as well as the possible existence of miRNA and mRNA interactions. We found that: i) the circRNA expression profile revealed 1,285 significant differences in circRNA expression, with circRNA expression downregulated in 594 samples and upregulated in 691 samples via interactions with miRNAs. The qRT-PCR validation experiments showed that hsa_circRNA_400071, hsa_circRNA_000543 and hsa_circRNA_001959 expression was consistent with the microarray analysis results. ii) 29,112 genes were found in the GC tissues and adjacent tissues, including 5,460 differentially expressed genes. Among them, 2,390 differentially expressed genes were upregulated and 3,070 genes were downregulated. Gene Ontology (GO) analysis of the differentially expressed genes revealed these genes involved in biological process classification, cellular component classification and molecular function classification. Pathway analysis of the differentially expressed genes identified 83 significantly enriched genes, including 28 upregulated genes and 55 downregulated genes. iii) 69 differentially expressed circRNAs were found that might adsorb specific miRNAs to regulate the expression of their target gene mRNAs. The conclusions are: i) differentially expressed circRNAs had corresponding miRNA binding sites. These circRNAs regulated the expression of target genes through interactions with miRNAs and might become new molecular biomarkers for GC in the future. ii) Differentially expressed genes may be involved in the occurrence of GC via a variety of mechanisms. iii) CD44, CXXC5, MYH9, MALAT1 and other genes may have important implications for the occurrence and development of GC through the regulation, interaction, and mutual influence of circRNA-miRNA-mRNA via different mechanisms.
本研究旨在筛选胃癌(GC)组织和癌旁组织中mRNA和环状RNA(circRNA)表达的差异,分析circRNA和mRNA表达的差异,并探究circRNA在胃癌中的表达及其机制。使用安捷伦微阵列技术分析GC组织和癌旁组织中产生的circRNA和mRNA差异表达谱。根据circRNA与微小RNA(miRNA)之间的相互作用以及miRNA和mRNA相互作用的可能存在情况,采用qRT-PCR验证circRNA和mRNA的差异表达。我们发现:i)circRNA表达谱显示circRNA表达存在1285个显著差异,通过与miRNA相互作用,594个样本中的circRNA表达下调,691个样本中的circRNA表达上调。qRT-PCR验证实验表明,hsa_circRNA_400071、hsa_circRNA_000543和hsa_circRNA_001959的表达与微阵列分析结果一致。ii)在GC组织和癌旁组织中发现了29112个基因,其中包括5460个差异表达基因。其中,2390个差异表达基因上调,3070个基因下调。对差异表达基因进行基因本体(GO)分析,发现这些基因涉及生物过程分类、细胞成分分类和分子功能分类。对差异表达基因进行通路分析,鉴定出83个显著富集的基因,其中28个上调基因和55个下调基因。iii)发现69个差异表达的circRNA可能吸附特定的miRNA以调节其靶基因mRNA的表达。结论如下:i)差异表达的circRNA具有相应的miRNA结合位点。这些circRNA通过与miRNA相互作用调节靶基因的表达,未来可能成为GC的新分子生物标志物。ii)差异表达基因可能通过多种机制参与GC的发生。iii)CD44、CXXC5、MYH9、MALAT1等基因可能通过circRNA-miRNA-mRNA的不同机制调控、相互作用和相互影响,对GC的发生发展具有重要意义。