Volume 24, Issue 101, January - February, 2020

CDK1 and PLK1 are key regulator proteins in human Papilloma virus Type 16-Positive Cervical Cancer: A Network-Based Study

Seyedeh Zahra Mousavi^1,2, Vahdat Poortahmasebi^3,4, Talat Mokhtari-Azad¹, Shohreh Shahmahmoodi¹, Somayeh Jalilvand^1♦, Ezatollah Rafiei Alavi⁵

¹Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
²Khoramabad Tamin Ejtemaee, Hospital, Lorestan, Iran
³Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
⁴Department of Bacteriology and Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
⁵Department of Patology, School of Medicine, Lorestan University of Medical Sciences, Lorestan, Iran

^♦Corresponding author
Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

ABSTRACT

Human papillomavirus (HPV) is the causative agent of cervical cancer. The purpose of present study was to provide a comprehensive protein-protein interaction (PPI) approach to identify the representative sub-networks for this cancer. Comprehensive gene expression profiling of cervical samples from different stages were collected from Gene Expression Omnibus (GEO-dataset: GSE67522). Among the three clinical stages, we generated two PPIs including, pre-cancerous network (normal-non-malignant) and cancerous network (non-malignant-CC or normal-CC). Subsequently, further bioinformatics analyses were performed. GO analysis revealed that the majority of differentially expressed genes in reconstructing cancerous networks was obviously involved in cell cycle processes. Serine/threonine kinases Polo-like kinase 1 (PLK1), cyclin-dependent kinase 1 (CDK1), and CDK2 were the most important hub genes in the protein-protein interaction network. These proteins play critical roles in the dysregulation of the cell cycle in cervical cancer development. Also, other cell cycle associated genes including AURKA, BRCA1, and CDC20 were all found highly critical genes in HPV16-infected cervical cancer. CDK1, CDK2 and PLK1 play essential roles in mediating integrative genetic networks involved in the development of cervical cancer. These hub genes might help improve pathogenesis of cervical cancer and may be used for the diagnosis and treatment of this cancer.

Keywords: Human papilloma virus, protein-protein interaction, cervical cancer, gene ontology, serine/threonine kinases Polo-like kinase 1, cyclin-dependent kinase 1

Medical Science, 2020, 24(101), 201-214

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