A systems approach for the elucidation of crucial genes and network constituents of cervical intraepithelial neoplasia 1 (CIN1)

Abstract

Cervical intra-epithelial neoplasia 1 (CIN1) is a pre-cancerous cervical cancer condition characterized by changes in the squamous cells of the cervix. Early detection may facilitate treatment as CIN1 may increase the risk of developing cervical cancer. An extensive system level analysis has been carried out to detect crucial network components of CIN1. Differential expression analysis was performed to identify genes that are differentially expressed in CIN1 in comparison to normal cells. Gene Ontology (GO) and pathway enrichment analyses of DEGs were followed by the construction of a protein–protein interaction (PPI) network. Hubs were identified and module enrichment analysis was performed. A gene regulatory network incorporating DEGs, microRNAs (miRNAs) and transcription factors (TFs) was constructed. To integrate these DEGs with the pathophysiology of CIN1, assessment of interaction of these gene/proteins and crucial motifs with statistical parameters such as z-score and p-value was carried out. Microarray analysis revealed 71 differentially expressed genes including 39 upregulated and 32 downregulated genes. 4 genes, namely PABPC1, RPS27, RPL13A and RPL21, were found to be overlapping among hubs and module genes of the PPI network and also part of the significant motifs of the regulatory network. Gene regulation of the DEGs also revealed important TFs and miRNAs such as ELF1, SRF, has-mir-125b-5p and has-mir-644a. PABPC1, RPS27, RPL13A and RPL21 may serve as potential biomarkers for CIN1 and as prospective targets for therapeutic approaches. Though, further experimental studies are required to confirm our findings.