Role and insights of human papillomavirus E5 oncoprotein in cervical carcinogenesis.

Cervical cancer is a highly prevalent malignancy affecting the health of women, and a leading cause of cancer-related mortality worldwide, particularly in low- and middle-income countries. The primary cause of cervical is persistent infection with high-risk human papillomavirus (HPV), particularly through the activation of its oncoproteins E6 and E7 that interact with host tumor suppressor genes. Another HPV oncoprotein, E5, has been reported to alter several tumorigenic signaling pathways; however, its precise role in cervical cancer has not yet been fully elucidated. Therefore, the aim of the present study was to perform a comprehensive in silico analysis to investigate the HPV-E5 associated hub genes and their associated signaling pathways. Five microarray datasets, namely GSE265111, GSE26888, GSE9750, GSE7803 and GSE5787 were retrieved from the Gene Expression Omnibus (GEO) database using 'HPV E5' and 'cervical cancer' as search terms. A total of 8,202 differentially expressed genes (DEGs) were common to all five datasets, from which the 10 hub genes, including several nucleoporins (NUPs) were identified. Kaplan-Meier analysis of these genes revealed that the expression of NUP85, NUP88 and NUP-like 1/NUP58 genes was associated with overall survival, suggesting the prognostic significance of these genes. In addition, three pairs of genes, specifically: NUP5 and NUP160; NUP50 and NUP98; and NUP160 and NUP98 were observed to exhibit significant co-occurrence, suggesting that they may be interdependent and involved in shared biological pathways in cervical cancer pathogenesis. Data from the Human Protein Atlas revealed that NUP50, NUP98 and NUP160 were differentially expressed in HPV-positive and -negative cervical cancer cell lines. The findings of the present study have improved our understanding of the potential role of HPV E5 in cervical carcinogenesis. However, further functional validation is necessary to confirm the findings.