miRNA and mRNA expression profiles in gastric cancer patients and the relationship with circRNA

Fei Jiang,  Xiao-Bing Shen

Abstract:

Gastric cancer (GC) is a malignant tumor that affects individuals worldwide, and miRNA and mRNA are closely connected to this disease. However, it is still unclear how these molecules affect GC and whether their effects are associated with circRNA in GC patients. Therefore, we obtained the miRNA, mRNA and circRNA expression profiles of GC patients from the GEO database. For comparison, shared miRNAs and mRNAs from the results of microarrays were annotated by gene ontology (GO) and pathway analysis. We also identified mRNAs that were targeted by miRNA through TargetScan 7.2 and circRNAs that were targeted by miRNA through CircInteractome. A comprehensive analysis of the microarray results revealed 72 shared miRNAs, and the expression profiles of 6 miRNAs were significantly different between the tumor and control groups (the absolute value of fold change >2, p<0.05). Hsa-miR-1, hsa-miR-142-3p, hsa-miR-95, hsa-miR-133a and hsa-miR-181d were upregulated in GC, whereas hsa-miR-375 was downregulated. The analysis results also revealed 1201 shared mRNAs and 27 mRNAs by microarray and TargetScan. Pathway analysis demonstrated that the Glypican pathway, Proteoglycan syndecan-mediated signaling events, Glypican 1 network and PAR1-mediated thrombin signaling events played important roles. GO analysis revealed significant enrichment in the three terms cellular component, molecular function and biological process, suggesting that organelles, enzyme binding, RNA-binding and nitrogen metabolism may have a strong relationship in GC. The increase in PAX6 in GC may be related to hsa-miR-375. Three circRNAs, hsa_circ_0001658, hsa_circ_0004928 and hsa_circ_0000376, were then found to be significantly differentially expressed between GC and normal tissues (the absolute value of fold change >2, p<0.05). In conclusion, the circ0001658/circ0004928/circ0000376-miR-375-PAX6 axis may represent a new regulatory network that should be further investigated, and the results of this study provide a better understanding of GC.