EREG, HOPX and SYNGR3 influence the Pathogenesis and Prognosis of Cervical Cancer through immune cells infiltration

Abstract

Abstract Background As a competitive endogenous RNA (ceRNA), circular RNA (circRNA) plays a significant role in the pathogenesis and progression of cervical cancer. A circRNA-associated ceRNA regulation network was built in this study, providing a new biological target for the treatment and prognosis of cervical cancer. Methods The expression profiles (GSE102686, GSE86100, and GSE7803) of circRNAs, miRNAs, and mRNAs were downloaded from the GEO database, and differentially expressed (DE) RNAs (DEcircRNAs, DEmiRNAs, and DEmRNAs) were acquired. The circRNA-miRNA and miRNA-mRNA regulatory links were retrieved from the CSCD and TargetScan databases, respectively. Then, a regulatory network for circRNA-associated ceRNA has been developed. On the basis of the ceRNA network, GO analysis, KEGG analysis, survival analysis, and sub-network creation were done. We verified the hub gene affecting prognosis through qRT-PCR. Finally, we analyzed the relationship between the four hub genes and immune cell infiltration in cervical cancer patients by the single sample gene set enrichment analysis method. Results A total of 13 DEcircRNAs, 330 DEmiRNAs, and 74 DEmRNAs were found, as well as 6 circRNA-miRNA pairings and 42 miRNA-mRNA pairings predicted. The ceRNA regulatory network (circRNA-miRNA-mRNA) was constructed, which included 3 circRNA, 4 miRNA, and 27 mRNA. The prognostic sub-network consists of 3 circRNAs (hsa_circ_0027821, hsa_circ_0046290, hsa_circ_0000745), 4 miRNAs (hsa-miR-766-3p, hsa-miR-96-5p, hsa-miR-362-5p, hsa-miR-1227-5p) and 4 mRNAs (CDA, EREG, HOPX and SYNGR3) that are associated with survival and prognosis of cervical cancer. Immune infiltration analysis shown that neutrophils were positively correlated with EREG gene and HOPX gene, but negatively correlated with SYNGR3 gene. Conclusions In this research, we established a circRNA-associated ceRNA regulation network for cervical cancer and discovered that hub genes (EREG, HOPX, and SYNGR3) influence the pathogenesis and clinical prognosis of cervical cancer by immune cells infiltration.