Integrated systems biology and structural approaches to discover novel biomarkers and small molecule inhibitors using the gene expression data from drug-resistant breast cancer cell lines
Breast cancer, the leading cause of cancer-related deaths in women, is driven by multidrug resistance, highlighting the urgent need for novel therapeutic targets. Consequently, we employed network-based gene expression profiling to analyse datasets from normal and tamoxifen-resistant MCF7 cell lines...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Journal of Taibah University for Science |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/16583655.2025.2541441 |
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| author | Suad A. Alghamdi Mohammed Alissa Muhammad Suleman |
| author_facet | Suad A. Alghamdi Mohammed Alissa Muhammad Suleman |
| author_sort | Suad A. Alghamdi |
| collection | DOAJ |
| description | Breast cancer, the leading cause of cancer-related deaths in women, is driven by multidrug resistance, highlighting the urgent need for novel therapeutic targets. Consequently, we employed network-based gene expression profiling to analyse datasets from normal and tamoxifen-resistant MCF7 cell lines. The analysis identified 372 DEGs, including 133 upregulated and 239 downregulated genes, with ISG15 emerging as the top hub gene. Survival analyses indicated that high ISG15 expression correlates with poorer overall survival in breast cancer. To identify potent inhibitors of ISG15, we screened an anticancer drug database and selected three top hits with docking scores of −6.6, −6.5 and −5.4 kcal/mol. Molecular dynamics simulations confirmed the dynamic stability and strong binding affinity of these top hits. The top hit (1-3) complexes showed favourable binding-free energies of −31.57, −23.92 and −28.05 kcal/mol, respectively, with desirable pharmacokinetic properties. This study highlights promising drug candidates targeting ISG15 in tamoxifen-resistant breast cancer, warranting further experimental validation. |
| format | Article |
| id | doaj-art-4ea7156aef6d4fa78e82efc6636b4d14 |
| institution | Kabale University |
| issn | 1658-3655 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Taibah University for Science |
| spelling | doaj-art-4ea7156aef6d4fa78e82efc6636b4d142025-08-20T03:44:52ZengTaylor & Francis GroupJournal of Taibah University for Science1658-36552025-12-0119110.1080/16583655.2025.2541441Integrated systems biology and structural approaches to discover novel biomarkers and small molecule inhibitors using the gene expression data from drug-resistant breast cancer cell linesSuad A. Alghamdi0Mohammed Alissa1Muhammad Suleman2Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi ArabiaDepartment of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi ArabiaCentre for Biotechnology and Microbiology, University of Swat, Swat, PakistanBreast cancer, the leading cause of cancer-related deaths in women, is driven by multidrug resistance, highlighting the urgent need for novel therapeutic targets. Consequently, we employed network-based gene expression profiling to analyse datasets from normal and tamoxifen-resistant MCF7 cell lines. The analysis identified 372 DEGs, including 133 upregulated and 239 downregulated genes, with ISG15 emerging as the top hub gene. Survival analyses indicated that high ISG15 expression correlates with poorer overall survival in breast cancer. To identify potent inhibitors of ISG15, we screened an anticancer drug database and selected three top hits with docking scores of −6.6, −6.5 and −5.4 kcal/mol. Molecular dynamics simulations confirmed the dynamic stability and strong binding affinity of these top hits. The top hit (1-3) complexes showed favourable binding-free energies of −31.57, −23.92 and −28.05 kcal/mol, respectively, with desirable pharmacokinetic properties. This study highlights promising drug candidates targeting ISG15 in tamoxifen-resistant breast cancer, warranting further experimental validation.https://www.tandfonline.com/doi/10.1080/16583655.2025.2541441Breast cancerdrug resistanceISG15System biologyMolecular dockingMolecular dynamics simulations |
| spellingShingle | Suad A. Alghamdi Mohammed Alissa Muhammad Suleman Integrated systems biology and structural approaches to discover novel biomarkers and small molecule inhibitors using the gene expression data from drug-resistant breast cancer cell lines Journal of Taibah University for Science Breast cancer drug resistance ISG15 System biology Molecular docking Molecular dynamics simulations |
| title | Integrated systems biology and structural approaches to discover novel biomarkers and small molecule inhibitors using the gene expression data from drug-resistant breast cancer cell lines |
| title_full | Integrated systems biology and structural approaches to discover novel biomarkers and small molecule inhibitors using the gene expression data from drug-resistant breast cancer cell lines |
| title_fullStr | Integrated systems biology and structural approaches to discover novel biomarkers and small molecule inhibitors using the gene expression data from drug-resistant breast cancer cell lines |
| title_full_unstemmed | Integrated systems biology and structural approaches to discover novel biomarkers and small molecule inhibitors using the gene expression data from drug-resistant breast cancer cell lines |
| title_short | Integrated systems biology and structural approaches to discover novel biomarkers and small molecule inhibitors using the gene expression data from drug-resistant breast cancer cell lines |
| title_sort | integrated systems biology and structural approaches to discover novel biomarkers and small molecule inhibitors using the gene expression data from drug resistant breast cancer cell lines |
| topic | Breast cancer drug resistance ISG15 System biology Molecular docking Molecular dynamics simulations |
| url | https://www.tandfonline.com/doi/10.1080/16583655.2025.2541441 |
| work_keys_str_mv | AT suadaalghamdi integratedsystemsbiologyandstructuralapproachestodiscovernovelbiomarkersandsmallmoleculeinhibitorsusingthegeneexpressiondatafromdrugresistantbreastcancercelllines AT mohammedalissa integratedsystemsbiologyandstructuralapproachestodiscovernovelbiomarkersandsmallmoleculeinhibitorsusingthegeneexpressiondatafromdrugresistantbreastcancercelllines AT muhammadsuleman integratedsystemsbiologyandstructuralapproachestodiscovernovelbiomarkersandsmallmoleculeinhibitorsusingthegeneexpressiondatafromdrugresistantbreastcancercelllines |