Metadata analysis to explore hub of the hub-genes highlighting their functions, pathways and regulators for cervical cancer diagnosis and therapies

Abstract

Abstract Cervical cancer (CC) is considered as the fourth most common women cancer globally.that shows malignant features of local infiltration and invasion into adjacent organs and tissues. There are several individual studies in the literature that explored CC-causing hub-genes (HubGs), however, we observed that their results are not so consistent. Therefore, the main objective of this study was to explore hub of the HubGs (hHubGs) that might be more representative CC-causing HubGs compare to the single study based HubGs. We reviewed 52 published articles and found 255 HubGs/studied-genes in total. Among them, we selected 10 HubGs (CDK1, CDK2, CHEK1, MKI67, TOP2A, BRCA1, PLK1, CCNA2, CCNB1, TYMS) as the hHubGs by the protein–protein interaction (PPI) network analysis. Then, we validated their differential expression patterns between CC and control samples through the GPEA database. The enrichment analysis of HubGs revealed some crucial CC-causing biological processes (BPs), molecular functions (MFs) and cellular components (CCs) by involving hHubGs. The gene regulatory network (GRN) analysis identified four TFs proteins and three miRNAs as the key transcriptional and post-transcriptional regulators of hHubGs. Then, we identified hHubGs-guided top-ranked FDA-approved 10 candidate drugs and validated them against the state-of-the-arts independent receptors by molecular docking analysis. Finally, we investigated the binding stability of the top-ranked three candidate drugs (Docetaxel, Temsirolimus, Paclitaxel) by using 100 ns MD-based MM-PBSA simulations and observed their stable performance. Therefore the finding of this study might be the useful resources for CC diagnosis and therapies.

Keywords

• Cervical cancer (CC)
• Hub genes (HubGs)
• Hub of the HubGs (hHubGs)
• Candidate drugs
• Integrated bioinformatics analysis