Novel transcripts of EMT driving the malignant transformation of oral submucous fibrosis
Abstract Oral submucous fibrosis (OSF) is a chronic, progressive, and fibrotic condition of the oral mucosa that carries an elevated risk of malignant transformation. We aimed to identify and validate novel genes associated with the regulation of epithelial-to-mesenchymal transition (EMT) in OSF. Ge...
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| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-87790-2 |
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| author | Smitha Sammith Shetty Kanaka Sai Ram Padam Mohit Sharma Adarsh Kudva Pratik Patel Raghu Radhakrishnan |
| author_facet | Smitha Sammith Shetty Kanaka Sai Ram Padam Mohit Sharma Adarsh Kudva Pratik Patel Raghu Radhakrishnan |
| author_sort | Smitha Sammith Shetty |
| collection | DOAJ |
| description | Abstract Oral submucous fibrosis (OSF) is a chronic, progressive, and fibrotic condition of the oral mucosa that carries an elevated risk of malignant transformation. We aimed to identify and validate novel genes associated with the regulation of epithelial-to-mesenchymal transition (EMT) in OSF. Genes regulating EMT were identified through differential gene expression analysis, using a LogFC threshold of -1 and + 1 and a padj value < 0.05, based on data from GEO datasets and the TCGA-HNSC datasets. The curated EMT genes were correlated with functional cancer states and subjected to clustering to identify candidate genes. Integration of bioinformatics and proteomics led to the discovery of the EMT genes MMP9, SPARC, and ITGA5 as novel candidates. Comprehensive pathway and immunohistochemical analyses confirmed their roles in regulating EMT in OSF, oral squamous cell carcinoma (OSCC), and OSF-associated squamous cell carcinoma (OSFSCC). The significant roles of MMP9, SPARC, and ITGA5 in fibrosis and malignancy suggest a novel mechanism in which fibrosis-associated type 2 EMT undergoes transition to type 3 EMT, driving OSF towards malignancy. |
| format | Article |
| id | doaj-art-d7d93ac6ee974b3a96391fb77b9b8bd6 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-d7d93ac6ee974b3a96391fb77b9b8bd62025-02-02T12:21:28ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-025-87790-2Novel transcripts of EMT driving the malignant transformation of oral submucous fibrosisSmitha Sammith Shetty0Kanaka Sai Ram Padam1Mohit Sharma2Adarsh Kudva3Pratik Patel4Raghu Radhakrishnan5Department of Oral and Maxillofacial Pathology and Microbiology, Manipal College of Dental Sciences, Manipal Academy of Higher EducationDepartment of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher EducationDepartment of Oral Pathology, SGT Dental College Hospital & Research InstituteDepartment of Oral and Maxillofacial Surgery, Manipal College of Dental Sciences, Manipal Academy of Higher EducationSangee Oral Pathology CenterDepartment of Oral and Maxillofacial Pathology and Microbiology, Manipal College of Dental Sciences, Manipal Academy of Higher EducationAbstract Oral submucous fibrosis (OSF) is a chronic, progressive, and fibrotic condition of the oral mucosa that carries an elevated risk of malignant transformation. We aimed to identify and validate novel genes associated with the regulation of epithelial-to-mesenchymal transition (EMT) in OSF. Genes regulating EMT were identified through differential gene expression analysis, using a LogFC threshold of -1 and + 1 and a padj value < 0.05, based on data from GEO datasets and the TCGA-HNSC datasets. The curated EMT genes were correlated with functional cancer states and subjected to clustering to identify candidate genes. Integration of bioinformatics and proteomics led to the discovery of the EMT genes MMP9, SPARC, and ITGA5 as novel candidates. Comprehensive pathway and immunohistochemical analyses confirmed their roles in regulating EMT in OSF, oral squamous cell carcinoma (OSCC), and OSF-associated squamous cell carcinoma (OSFSCC). The significant roles of MMP9, SPARC, and ITGA5 in fibrosis and malignancy suggest a novel mechanism in which fibrosis-associated type 2 EMT undergoes transition to type 3 EMT, driving OSF towards malignancy.https://doi.org/10.1038/s41598-025-87790-2Oral squamous cell carcinomaOral submucous fibrosisCandidate genesEMTIn-silico analysisProteomics |
| spellingShingle | Smitha Sammith Shetty Kanaka Sai Ram Padam Mohit Sharma Adarsh Kudva Pratik Patel Raghu Radhakrishnan Novel transcripts of EMT driving the malignant transformation of oral submucous fibrosis Scientific Reports Oral squamous cell carcinoma Oral submucous fibrosis Candidate genes EMT In-silico analysis Proteomics |
| title | Novel transcripts of EMT driving the malignant transformation of oral submucous fibrosis |
| title_full | Novel transcripts of EMT driving the malignant transformation of oral submucous fibrosis |
| title_fullStr | Novel transcripts of EMT driving the malignant transformation of oral submucous fibrosis |
| title_full_unstemmed | Novel transcripts of EMT driving the malignant transformation of oral submucous fibrosis |
| title_short | Novel transcripts of EMT driving the malignant transformation of oral submucous fibrosis |
| title_sort | novel transcripts of emt driving the malignant transformation of oral submucous fibrosis |
| topic | Oral squamous cell carcinoma Oral submucous fibrosis Candidate genes EMT In-silico analysis Proteomics |
| url | https://doi.org/10.1038/s41598-025-87790-2 |
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