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Metadata analysis to explore hub of the hub-genes highlighting their functions, pathways and regulators for cervical cancer diagnosis and therapies
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 observe...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9395557/ https://www.ncbi.nlm.nih.gov/pubmed/35994213 http://dx.doi.org/10.1007/s12672-022-00546-6 |
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author | Reza, Md. Selim Hossen, Md. Alim Harun-Or-Roshid, Md. Siddika, Mst. Ayesha Kabir, Md. Hadiul Mollah, Md. Nurul Haque |
author_facet | Reza, Md. Selim Hossen, Md. Alim Harun-Or-Roshid, Md. Siddika, Mst. Ayesha Kabir, Md. Hadiul Mollah, Md. Nurul Haque |
author_sort | Reza, Md. Selim |
collection | PubMed |
description | 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-022-00546-6. |
format | Online Article Text |
id | pubmed-9395557 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-93955572022-08-24 Metadata analysis to explore hub of the hub-genes highlighting their functions, pathways and regulators for cervical cancer diagnosis and therapies Reza, Md. Selim Hossen, Md. Alim Harun-Or-Roshid, Md. Siddika, Mst. Ayesha Kabir, Md. Hadiul Mollah, Md. Nurul Haque Discov Oncol Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-022-00546-6. Springer US 2022-08-22 /pmc/articles/PMC9395557/ /pubmed/35994213 http://dx.doi.org/10.1007/s12672-022-00546-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Reza, Md. Selim Hossen, Md. Alim Harun-Or-Roshid, Md. Siddika, Mst. Ayesha Kabir, Md. Hadiul Mollah, Md. Nurul Haque Metadata analysis to explore hub of the hub-genes highlighting their functions, pathways and regulators for cervical cancer diagnosis and therapies |
title | Metadata analysis to explore hub of the hub-genes highlighting their functions, pathways and regulators for cervical cancer diagnosis and therapies |
title_full | Metadata analysis to explore hub of the hub-genes highlighting their functions, pathways and regulators for cervical cancer diagnosis and therapies |
title_fullStr | Metadata analysis to explore hub of the hub-genes highlighting their functions, pathways and regulators for cervical cancer diagnosis and therapies |
title_full_unstemmed | Metadata analysis to explore hub of the hub-genes highlighting their functions, pathways and regulators for cervical cancer diagnosis and therapies |
title_short | Metadata analysis to explore hub of the hub-genes highlighting their functions, pathways and regulators for cervical cancer diagnosis and therapies |
title_sort | metadata analysis to explore hub of the hub-genes highlighting their functions, pathways and regulators for cervical cancer diagnosis and therapies |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9395557/ https://www.ncbi.nlm.nih.gov/pubmed/35994213 http://dx.doi.org/10.1007/s12672-022-00546-6 |
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