Circular RNA Expression Profile in Cervical Cancer and Construction of the Circular RNA‑MicroRNA‑Messenger RNA Regulatory Network

Abstract

Introduction. Cervical cancer (CC) remains the most common cancer in women worldwide. However, effective and specific biomarkers for the diagnosis and prognosis of cervical cancer are yet to be found. In recent years, the potential of circular RNAs (circRNAs) as new diagnostic, prognostic and therapeutic tools has received much attention. The current study involved an in-depth bioinformatics research to explore the circRNA-microRNA (miRNA)-messenger RNA (mRNA) regulatory network in order to identify important molecular processes and biological pathways supposedly associated with CC. Materials and methods. The study collected data on the expression of circRNA (GSE102686), miRNA (GSE30656) and mRNA of target genes (GSE9750), based on the Gene Expression Omnibus (GEO) database, in squamous cell carcinoma of the cervix samples and normal squamous epithelium of the cervix, dividing them into study and control groups. Protein-protein interaction (PPI), Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to further understand the function of circRNAs for their target genes. Results. A total of 105 differentially expressed circular RNAs (DECs), 144 differentially expressed microRNAs (DEMs), and 539 differentially expressed target genes (DEGs) were identified for cervical cancer. Concurrently, functional enrichment analysis of GO and KEGG pathways was performed for DEGs. Subsequently, searching databases for circRNA, miRNA and mRNA target genes, as well as PPI network analysis and functional enrichment revealed 3 DECs with significantly high expression levels (hsa_circ_0000745, hsa_circ_0084927 and hsa_circ_0002762), 6 DEMs with reduced expression levels (hsa -miR-145, hsa-miR-876-3p, hsa-miR-1229, hsa-miR-182, hsa-miR-520h and hsa-miR-1252) and 9 key genes such as ANGPT2, COL11A1, MEST, KIF20A, CLN6, FNDC3B, USP18, DLGAP5 and CXCL9, suggesting a potentially significant role in cervical cancer. Conclusion.Understanding the circRNA-miRNA-mRNA regulatory network is of great importance for evaluating the oncogenesis of CC, as well as discoverying new circRNAs as the main regulatory molecules in this network. This is considered to be a new direction in the diagnosis and targeted therapy of cervical cancer.