Bioinformatics analyses reveal differential expression and potential function of circular RNAs as efficient microRNA sponges in gastric cancer

Introduction & objectives: Gastric cancer (GC) is one of the most common malignant tumors worldwide. Circular RNAs (circRNAs) are a class of non-coding RNAs that due to their beneficial properties like being usually abundant, conserved and stable, expected to be biomarkers for early diagnosis of different cancers. The most prominent function of circRNAs is their actions as microRNA (miRNA) sponge to regulate target gene expression. The current study aimed to identify differentially expressed circRNAs in GC and evaluate their sponge-related functions. Materials & Methods: Three GC gene expression datasets (GSE78092, GSE83521 and GSE89143) were downloaded from Gene Expression Omnibus (GEO). Using GEO2R tool, differentially expressed circRNAs (DECis) with adj p-value<0.05 and │logFC│>1 were filtered out. DECis existing at least in two datasets and with same direction of gene expression changes were then selected. CircInteractome was explored to find interacting miRNAs. Additionally, DIANA-miRPath was exploited to identify molecular pathways potentially mediated by these interacting miRNAs. Results: Using the cut-off criteria, 287 DECis were identified. Three circRNAs including hsa_circ_0000981, hsa_circ_0008301 and hsa_circ_0021087 were existed at least in two datasets with a decreased expression in tumoral compared to non-tumoral gastric tissues. CircInteractome showed 35 miRNAs are totally interacted with these three circRNAs. A total of 31 statistically significant KEGG pathways were obtained from the analysis of target genes of interacting miRNAs. We found that the predicted target genes of interacting miRNAs are mostly associated with crucial cancer-related pathways like Hippo signaling pathway, viral carcinogenesis, cell cycle, adherens junction and transcriptional misregulation. Conclusion: According to GEO datasets, a comprehensive expression profile of differentially expressed circRNAs was revealed in gastric cancer. Gene enrichment analysis predicted that these circRNAs and their associated miRNAs are involved in multiple cancer-associated pathways. Further investigations are needed to unravel the precise mechanism of action of circRNAs in cancer pathogenesis.

کلیدواژه ها:

Circular RNA ، Gastric cancer ، microRNA ، Sponge