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Novel Transcripts of EMT Driving the Malignant Transformation of Oral Submucous Fibrosis [Whole transcriptome]

ABSTRACT: Novel Transcripts of EMT Driving the Malignant Transformation of Oral Submucous Fibrosis [Whole transcriptome]

PROVIDER: PRJNA1145396 | ENA |

REPOSITORIES: ENA

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Novel Transcripts of EMT Driving the Malignant Transformation of Oral Submucous Fibrosis [Whole transcriptome]

Project description:OSF is a chronic, progressive, fibrotic condition of the oral mucosa that carries an elevated risk of undergoing malignant transformation. We aimed to identify and validate novel genes associated with the regulation of epithelial to mesenchymal transition (EMT) in Oral submucous fibrosis (OSF). Genes regulating EMT were identified through differential gene expression analysis, with a LogFC threshold of -1 and +1, and padj value < 0.05, utilizing data retrieved from GEO datasets, TCGA-HNSC dataset and whole transcriptome data generated from tissue samples of OSF, OSFSCC (OSF associated with OSCC) and OSCC (Oral squamous cell carcinoma). The curated EMT genes were correlated with functional states of cancer, subjected to clustering to identify the candidate genes. The EMT genes, namely MMP9, SPARC and ITGA5 were identified to be the novel candidate genes. Comprehensive pathway analysis and immunohistochemical analysis confirmed their role in regulating EMT in OSF, OSCC, and OSFSCC. Integration of bioinformatics and proteomics led to the discovery of novel candidate genes regulating EMT. The significant role of candidate genes MMP9, SPARC, and ITGA5 observed in fibrosis and malignancy indicates a novel mechanism of transition from fibrosis associated type 2 EMT to type 3 EMT, driving OSF to malignancy.

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Project description:This SuperSeries is composed of the following subset Series: GSE32727: EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors [human] GSE32904: EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors [mouse] Refer to individual Series

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Project description:Oral submucous fibrosis (OSF) as one of the malignant disorders endures a series of histopathological stages to invasive oral squamous cell carcinoma (OSCC) eventually. The role of long non-coding RNA (lncRNA) expression in OSF malignant progression is still poorly understood. Genome-wide lncRNA expression profiling of normal mucous, OSF and OSCC tissues was performed by RNA sequencing. Bioinformatic methods were applied for differential lncRNA analysis and functional enrichment analysis. Quantitative-RT-PCR was used to verify identified lncRNAs.21 novel transcripts were differentially expressed among all three stages during OSF progression with varied expression levels. Our study firstly comprehensively elucidated lncRNAs expression profile of the process of OSCC premalignant lesion to OSCC.

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Evaluation of PTEN immunoexpression in oral submucous fibrosis: role in pathogenesis and malignant transformation.

Project description:Oral submucous fibrosis (OSMF) is a chronic debilitating disease and a premalignant condition of the oral cavity characterized by generalized submucosal fibrosis. Despite its precancerous nature, the molecular biology regarding its malignant potential has not been extensively studied. PTEN, a known tumor suppressor gene is mutated in a majority of human cancers and has also been implicated in several fibrotic disorders. The present study aims to evaluate the expression of PTEN in OSMF and oral squamous cell carcinoma (OSCC) and correlate it with the pathogenesis and malignant transformation of OSMF. 60 cases total of OSMF (30) and OSCC (30) were subjected to immunohistochemistry using PTEN antibody. Ten normal oral mucosa (NOM) specimens were also stained as controls. There was progressive loss of PTEN expression from normal mucosa to OSMF and OSCC (p ? 0.001). Significant differences were observed for PTEN expression between NOM and OSMF, OSMF and OSCC as well as NOM and OSCC. Though a progressive loss of PTEN was noticed between early OSMF and advanced OSMF, the variation did not reach statistical significance (p ? 0.001). Data suggest that there is a significant loss of PTEN expression in OSMF as compared to normal oral mucosa and that this trend increased from OSMF to OSCC. Thus, alteration of PTEN is likely an important molecular event in OSMF pathogenesis and oral carcinogenesis.

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