Alterations in miRNA Expression and Their Role in the Pathogenesis of Cervical Cancer.

Abstract

Cervical cancer has a high incidence and mortality rate, affecting more than half a million women in 2018. Its development is strongly related to high-risk HPV infection. After infection, several cellular molecules are affected, including microRNAs (miRNAs), which are the focus of our study. We aimed to investigate changes in microRNA expression associated with cervical cancer and analyze the biological significance of these changes induced by HPV proteins. We analyzed transcriptome data retrieved from the NCBI website to investigate miRNA and gene expression in cervical cancer. We evaluated the alteration in expression of miRNAs and genes (between normal tissues and cervical cancer) using the GEO2R tool and selected those with significantly altered expression (p-value < 0.05). The target genes of miRNAs were predicted using the miRNA Pathway Dictionary Database. Subsequently, we created a network of biological pathways affected by miRNA deregulation using Cytoscape software and associated the altered miRNAs with the Hallmarks of Cancer using COSMIC v84. We identified 10 miRNAs and 82 target genes with significantly altered expression levels in cervical cancer that matched the predicted results. In addition, the deregulation of these genes causes changes in 52 biological pathways. These miRNAs affected pathways such as interferon signaling (miR-106b-5p and miR-1183), signaling by interleukins (miR-557, miR-106b-5p, miR-15a-5p, and miR-21-5p), oxidative stress-induced senescence (miR-557 and miR-15a-5p), cell cycle checkpoints (miR-557), transcriptional regulation by P53 (miR-557 and miR-15a-5p), and the exchange of oxygen and carbon dioxide in erythrocytes (miR-15a-5p). Alterations in miRNA expression play an important role in the pathogenesis of cervical cancer, affecting several biological pathways and Hallmarks of Cancer, such as immune system regulation, cell cycle regulation, and energy metabolism. Thus, their analysis can contribute to the development of diagnostic and prognostic biomarkers and more effective treatments for cervical cancer.