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Long non-coding RNA expression profile associated with malignant progression of oral submucous fibrosis

ABSTRACT: Long non-coding RNA expression profile associated with malignant progression of oral submucous fibrosis

PROVIDER: PRJNA517729 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8503820_1.fastq.gz	Fastqsanger.gz
	SRR8503820_2.fastq.gz	Fastqsanger.gz
	SRR8503811_1.fastq.gz	Fastqsanger.gz
	SRR8503811_2.fastq.gz	Fastqsanger.gz
	SRR8503821_1.fastq.gz	Fastqsanger.gz

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Long non-coding RNA expression profile associated with malignant progression of oral submucous fibrosis

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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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:Novel Transcripts of EMT Driving the Malignant Transformation of Oral Submucous Fibrosis [mRNA-seq]

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Long Non-Coding RNA Expression Profile Associated with Malignant Progression of Oral Submucous Fibrosis.

Project description:Oral submucous fibrosis (OSF) as one of the premalignant disorders endures a series of histopathological stages to invasive oral squamous cell carcinoma (OSCC) eventually. However, the role of long non-coding RNA (lncRNA) expression in OSF malignant progression still remains poorly understood. Through RNA-sequencing normal mucous, OSF and OSCC tissues, we found 687 lncRNA transcripts significantly and differentially expressed during OSF progression, including 231 upregulated lncRNAs and 456 downregulated lncRNAs, indicating that lncRNAs are involved in the regulation of different stages of OSF development. Further functional enrichment analysis showed these differentially expressed lncRNAs participated in inflammation signaling, Wnt signaling, angiogenesis, CCKR signaling, integrin signaling, PDGF signaling, p53 signaling, and EGF receptor (EGFR) signaling pathways, which contribute to inflammatory and fibroelastic pathogenetic changes of OSF and further malignant progression. Five novel lncRNAs were differentially expressed during OSF progression with varied expression levels, indicating the importance of these lncRNAs in OSF malignant development. Moreover, some lncRNAs have been previously identified to be associated with OSCC pathogenesis, including HCG22, RP11-397A16.1, LINC00271, CTD-3179P9.1, and ZNF667-AS1. Thus, our study firstly comprehensively elucidated lncRNAs expression profile of malignant procession from OSF premalignant lesion to OSCC, which will enlighten our understanding of the importance of lncRNA involved in OSF malignant development.

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