OSI-027 as a Potential Drug Candidate Targeting Upregulated Hub Protein TAF1 in Potential Mechanism of Sinonasal Squamous Cell Carcinoma: Insights from Proteomics and Molecular Docking
Sinonasal squamous cell carcinoma (SNSCC) is a rare tumor with high mortality and recurrence rates. However, SNSCC carcinogenesis mechanisms and potential therapeutic drugs have not been fully elucidated. This study investigated the key molecular mechanisms and hub proteins involved in SNSCC carcino...
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2024-12-01
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| author | Watcharapong Panthong Chamsai Pientong Thawaree Nukpook Chukkris Heawchaiyaphum Sirinart Aromseree Tipaya Ekalaksananan |
| author_facet | Watcharapong Panthong Chamsai Pientong Thawaree Nukpook Chukkris Heawchaiyaphum Sirinart Aromseree Tipaya Ekalaksananan |
| author_sort | Watcharapong Panthong |
| collection | DOAJ |
| description | Sinonasal squamous cell carcinoma (SNSCC) is a rare tumor with high mortality and recurrence rates. However, SNSCC carcinogenesis mechanisms and potential therapeutic drugs have not been fully elucidated. This study investigated the key molecular mechanisms and hub proteins involved in SNSCC carcinogenesis using proteomics and bioinformatic analysis. Dysregulated proteins were validated by RT-qPCR in SNSCC and nasal polyp (NP) tissues. Proteomic analysis revealed that differentially expressed proteins were clustered using MCODE scores ≥ 4 into three modules. The specific hub proteins in each module were analyzed in carcinogenesis pathways using STRING, highlighting potential mechanisms of histone modification and spliceosome dysregulation. Spliceosome components SNRNP200 and SF3A3 were significantly downregulated in SNSCC by RT-qPCR. Web-based applications L1000CDS<sup>2</sup> and iLINCS were applied to identify 10 potential repurposable drugs that could reverse the gene expression pattern associated with SNSCC. Docking studies of TAF1, a protein in histone modification, with these 10 small molecule inhibitors indicated OSI-027 to be the most promising due to its strong binding interactions with key residues. These findings suggest that hub proteins involved in the underlying mechanism of SNSCC carcinogenesis may serve as valuable targets for drug development, with OSI-027 emerging as a novel candidate against TAF1 in SNSCC. |
| format | Article |
| id | doaj-art-e8cfb49e13894d95a213af559c41ff81 |
| institution | OA Journals |
| issn | 2079-7737 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
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| series | Biology |
| spelling | doaj-art-e8cfb49e13894d95a213af559c41ff812025-08-20T02:01:04ZengMDPI AGBiology2079-77372024-12-011312108910.3390/biology13121089OSI-027 as a Potential Drug Candidate Targeting Upregulated Hub Protein TAF1 in Potential Mechanism of Sinonasal Squamous Cell Carcinoma: Insights from Proteomics and Molecular DockingWatcharapong Panthong0Chamsai Pientong1Thawaree Nukpook2Chukkris Heawchaiyaphum3Sirinart Aromseree4Tipaya Ekalaksananan5Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandSinonasal squamous cell carcinoma (SNSCC) is a rare tumor with high mortality and recurrence rates. However, SNSCC carcinogenesis mechanisms and potential therapeutic drugs have not been fully elucidated. This study investigated the key molecular mechanisms and hub proteins involved in SNSCC carcinogenesis using proteomics and bioinformatic analysis. Dysregulated proteins were validated by RT-qPCR in SNSCC and nasal polyp (NP) tissues. Proteomic analysis revealed that differentially expressed proteins were clustered using MCODE scores ≥ 4 into three modules. The specific hub proteins in each module were analyzed in carcinogenesis pathways using STRING, highlighting potential mechanisms of histone modification and spliceosome dysregulation. Spliceosome components SNRNP200 and SF3A3 were significantly downregulated in SNSCC by RT-qPCR. Web-based applications L1000CDS<sup>2</sup> and iLINCS were applied to identify 10 potential repurposable drugs that could reverse the gene expression pattern associated with SNSCC. Docking studies of TAF1, a protein in histone modification, with these 10 small molecule inhibitors indicated OSI-027 to be the most promising due to its strong binding interactions with key residues. These findings suggest that hub proteins involved in the underlying mechanism of SNSCC carcinogenesis may serve as valuable targets for drug development, with OSI-027 emerging as a novel candidate against TAF1 in SNSCC.https://www.mdpi.com/2079-7737/13/12/1089sinonasal squamous cell carcinomaproteomicspliceosomerepurposing drugOSI-027 |
| spellingShingle | Watcharapong Panthong Chamsai Pientong Thawaree Nukpook Chukkris Heawchaiyaphum Sirinart Aromseree Tipaya Ekalaksananan OSI-027 as a Potential Drug Candidate Targeting Upregulated Hub Protein TAF1 in Potential Mechanism of Sinonasal Squamous Cell Carcinoma: Insights from Proteomics and Molecular Docking Biology sinonasal squamous cell carcinoma proteomic spliceosome repurposing drug OSI-027 |
| title | OSI-027 as a Potential Drug Candidate Targeting Upregulated Hub Protein TAF1 in Potential Mechanism of Sinonasal Squamous Cell Carcinoma: Insights from Proteomics and Molecular Docking |
| title_full | OSI-027 as a Potential Drug Candidate Targeting Upregulated Hub Protein TAF1 in Potential Mechanism of Sinonasal Squamous Cell Carcinoma: Insights from Proteomics and Molecular Docking |
| title_fullStr | OSI-027 as a Potential Drug Candidate Targeting Upregulated Hub Protein TAF1 in Potential Mechanism of Sinonasal Squamous Cell Carcinoma: Insights from Proteomics and Molecular Docking |
| title_full_unstemmed | OSI-027 as a Potential Drug Candidate Targeting Upregulated Hub Protein TAF1 in Potential Mechanism of Sinonasal Squamous Cell Carcinoma: Insights from Proteomics and Molecular Docking |
| title_short | OSI-027 as a Potential Drug Candidate Targeting Upregulated Hub Protein TAF1 in Potential Mechanism of Sinonasal Squamous Cell Carcinoma: Insights from Proteomics and Molecular Docking |
| title_sort | osi 027 as a potential drug candidate targeting upregulated hub protein taf1 in potential mechanism of sinonasal squamous cell carcinoma insights from proteomics and molecular docking |
| topic | sinonasal squamous cell carcinoma proteomic spliceosome repurposing drug OSI-027 |
| url | https://www.mdpi.com/2079-7737/13/12/1089 |
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