Circular RNA and gene expression profiles in gastric cancer based on microarray chip technology

Abstract

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.

Functional role of circular RNAs in cancer development and progression

“…Recently, a study on gastric cancer (GC) tissues identified a network of circRNA, miRNA and mRNAs that are differentially expressed between the GC tissues and adjacent normal tissue samples [94]. This raises a possibility of a direct linkage between the regulatory properties among the network of circRNA-miRNA-mRNA expressions.…”

Circular RNA hsa_circ_0000567 can be used as a promising diagnostic biomarker for human colorectal cancer

“…Emerging evidence has indicated that circRNAs are involved in many pathophysiological processes in many human diseases . In the study field of tumorigenesis and progression, recent studies have revealed that certain circRNAs are deregulated in many kinds of human cancers through high‐throughput RNA sequencing, such as gastric cancer, breast cancer, basal cell carcinoma, and cutaneous squamous cell carcinoma . Furthermore, several aberrant circRNAs have been identified as oncogenes or tumor suppressors .…”

Molecular Crosstalking among Noncoding RNAs: A New Network Layer of Genome Regulation in Cancer

“…Most reports that connect circRNAs and tumors mainly concern comparative gene expression profiling studies between tumor and normal samples. These investigations have shown that circRNAs are frequently downregulated in several types of cancer (e.g., colorectal cancer, ovarian cancer, and gastric cancer) [64–66]. Just few of these studies attempted to functionally explain how abnormal expression of circRNAs could impair physiological cell homeostasis and thus promote cancer phenotypes [67–69].…”