Expression of m6A methylation-modified circRNA in malignant transformation of oral leukoplakia tissue
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PROVIDER: PRJNA1016357 | ENA |
REPOSITORIES: ENA
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Project description:Objective This study aimed to investigate the expression and clinical significance of N6-methyladenosine (m6A) modification of circular RNA (circRNA) in oral leukoplakia (OLK) and oral squamous carcinoma cell (OSCC) tissues. Methods Using methylation RNA immunoprecipitation high-throughput sequencing technology (MeRIP-seq) and RNA high-throughput sequencing technology (RNA-seq), the first circRNA transcriptome analysis for detecting m6A methylationome profiles in OLK and OSCC tissues was obtained, followed by bioinformatics analysis. The qRT-PCR technique and protein immunoblotting technique were used to detect the expression of m6A methylesterase in OLK versus OSCC tissues. Results In this study, 275 differential m6A methylation peaks were identified in OLK and OSCC, among which 193 peaks were up-regulated and 82 were down-regulated. Additionally, 198 differential m6A methylation modified circRNAs were observed, with 127 up-regulated and 71 down-regulated (FC ≥ 2, P < 0.05). Most of the identified circRNAs that underwent m6A methylation alterations were derived from overlapping regions. It was found that the differential expression of circRNAs was not correlated with the joint analysis of significantly different m6A-circRNAs between the two groups. Furthermore, downregulation of mETTL14 and FTO protein levels was observed in OSCC tissues, although there were no discernible alterations in RNA levels. Conclusion Our study suggests that m6A methylation modification of circRNA may play a role in the development of oral leukoplakia, and that METTL14 and FTO may be important methylation enzymes that influence the development of oral leukoplakia. These findings may open up new research directions for in-depth investigations to clarify the molecular mechanisms of OLK carcinogenesis.
2023-09-20 | GSE243097 | GEO
Project description:Proliferative verrucous leukoplakia (PVL) is a potentially malignant disorder characterized by contiguous spread, a spectrum of clinicopathological features and high malignant transformation risk. Despite many efforts to describe the clinicopathological features of PVL progression, so far, there is still a lack of knowledge on the dynamic changes in molecular signature during this process. Hence, we applied single-cell RNA sequencing to 3 biopsy samples from a large PVL lesion. These samples exhibited the histopathological continuum of PVL lesions progression. By analysis for transcriptome profiling of 27,611 cells from these samples, we identified 10 major cell lineages and revealed the cellular remodeling occurring in the progression of PVL lesions, including epithelial, stromal and immune cells. The epithelial cells are shifted to pro-tumorigenic transcriptional cell states and secretory patterns at premalignant stage. Immune cells showed growing immunosuppressive phenotypes during PVL progression. Remarkably, two novel cell subtypes INSR+ endothelial cells and ASPN+ fibroblasts were discovered and may play a vital role in microenvironment remodeling, such as angiogenesis and stromal fibrosis, closely involved in the malignant transformation. Our work preliminarily describes the dynamic molecular properties of PVL lesions, enhances the systematic understanding of the premalignant evolution of PVL and attempts to provide the framework for future research.
2024-01-31 | GSE196296 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE38926: Patterns of aberrant DNA methylation after toxicant-induced malignant transformation (MeDIP-chip dataset 1) GSE38928: Patterns of aberrant DNA methylation after toxicant-induced malignant transformation (MeDIP-chip dataset 2) GSE38929: Patterns of aberrant DNA methylation after toxicant-induced malignant transformation (miRNA dataset) Refer to individual Series
2012-06-25 | E-GEOD-38930 | biostudies-arrayexpress
Project description:Gene expression changes associated with malignant transformation of oral potentially malignant disorders
| PRJNA657049 | ENA
Project description:Arsenic is environmental risk factor and has been linked to urothelial carcinoma incidence. Arsenic exposure-induced malignant transformed cells was established from normal urothelial cells by chronic arsenic exposure for 10 months. The purpose of the present study is to elucidate the relevant molecular alterationon on arsenic-induced malignant transformation.
2016-11-19 | GSE90023 | GEO
Project description:BackgroundMost oral squamous cell carcinomas (OSCC) occur on the basis of oral leukoplakias (OLP). The histologic degree of dysplasia is insufficient for the prediction of OLP malignant transformation. Immunologic parameters are gaining importance for prognostic assessment and therapy of cancer. M2 polarized macrophages were shown to be associated with OSCC progression and inferior prognosis. The current study aims to answer the question if OLP with malignant transformation into OSCC within 5 years differ from OLP without transformation regarding macrophage infiltration and polarization.Methods201 specimens (50 transforming OLP, 53 non-transforming OLP, 49 corresponding OSCC and 49 healthy oral mucosa controls) were processed for immunohistochemistry. Samples were stained for CD68, CD163 and CD11c expression, completely digitalized and computer-assisted cell counting was performed. Epithelial and subepithelial compartments were differentially assessed. Groups were statistically compared using the Mann-Whitney U-test. A cut-off point for the discrimination of transforming and non-transforming OLP was determined and the association between macrophage infiltration and malignant transformation was calculated using the Chi-square test (χ2 test).ResultsMacrophage infiltration and M2 polarization in OLP with malignant transformation within 5 years was significantly increased compared to OLP without malignant transformation (p < 0.05). OSCC samples showed the highest macrophage infiltration and strongest M2 polarization (p < 0.05). Additionally, transforming OLP revealed a significant shift of macrophage infiltration towards the epithelial compartment (p < 0.05). χ2 test revealed a significant association of increased macrophage infiltration with malignant transformation (p < 0.05).ConclusionImmunological changes precede malignant transformation of OLP. Increased macrophage infiltration and M2 polarization was associated with the development of oral cancer in OLP. Macrophage infiltration could serve as predictive marker for malignant transformation.
| S-EPMC6945578 | biostudies-literature
Project description:LPS-mediated noncoding RNA IFITM4P promotes malignant progression of oral leukoplakia through nucleocytoplasmic shuttling
| PRJNA704081 | ENA
Project description:A large number of oral squamous cell carcinomas (OSCCs) are believed to be preceded by oral potentially malignant disorders (OPMD) that have an increased likelihood of malignant transformation compared to clinically normal mucosa. This study was performed to identify differentially expressed genes between OPMDs that underwent malignant transformation (MT) and those that did not, termed ‘non-transforming’ (NT) cases. Total RNA was extracted from formalin-fixed paraffin-embedded tissue biopsies of 20 OPMD cases with known clinical outcomes (10 MT vs. 10 NT). Samples were assessed for quantity, quality and integrity of RNA prior to sequencing. Analysis for differential gene expression between MT and NT was performed using statistical packages in R. Genes were considered to be significantly differentially expressed if the False Discovery Rate corrected p-value was < 0.05. RNA yield was variable but RNA purity was good (A260/A280 >1.90). Analysis of RNA-Sequencing outputs revealed 41 genes (34 protein-coding; 7 non-coding) that were significantly differentially expressed between MT and NT cases. The log2 fold change for the statistically significant differentially expressed genes ranged from -2.63 to 2.48, with 23 protein-coding genes being downregulated and 11 protein-coding genes being upregulated in MT cases compared to NT cases. Several candidate genes that may play a role in malignant transformation of OPMD have been identified. Experiments to validate these candidates are underway. It is anticipated that this work will contribute to better understanding of the aetiopathogenesis of OPMD and development of novel biomarkers.
2020-08-14 | GSE156208 | GEO
Project description:Genomewide DNA methylation profiling of oral leukoplakia and oral sqamous cell carcinoma (OSCC) was performed to delineate candidate gene associated with progression and clinicopathological parameters. All tissue samples were collected after obtaining written informed consent. The DNA methylation profile of 74 OSCC and 22 leukoplakia were compared with 22 normal control tissues from healthy donor.
2023-06-05 | GSE204943 | GEO
Project description:Mastitis is a common disease that hinders the development of dairy industry and animal husbandry. It leads to the abuse of antibiotics, the emergence of super drug-resistant bacteria, and poses a great threat to human food health and safety. Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) are the most common pathogens of mastitis in dairy cows and usually cause subclinical or clinical mastitis. CircRNAs and N6-methyladenosine (m6A) play important roles in immunological diseases. However, the mechanisms by which m6A modifies circRNA in bovine mammary epithelial cells remain poorly understood. The aim of our study was to investigate m6A-modified circRNAs in bovine mammary epithelial cells (MAC-T cells) injured by S. aureus and E. coli. The profile of m6A-modified circRNA showed a total of 1599 m6A peaks within 1035 circRNAs in the control group, 35 peaks within 32 circRNAs in the S. aureus group, and 1016 peaks within 728 circRNAs in the E. coli group. Compared with the control group, 67 peaks within 63 circRNAs were significantly different in the S. aureus group, and 192 peaks within 137 circRNAs were significantly different in the E. coli group. Furthermore, we found the source genes of these differentially m6A-modified circRNAs in the S. aureus and E. coli groups with similar functions according to GO and KEGG analyses, which were mainly associated with cells injury, such as inflammation, apoptosis, and autophagy. CircRNA-miRNA-mRNA interaction networks predicted the potential circRNA regulation mechanism in S. aureus- and E. coli-induced cell injury. We found that the mRNAs in the networks, such as BCL2, MIF and TNFAIP8L2, greatly participated in the MAPK, WNT, and inflammation pathways. This is the first report on m6A-modified circRNA regulation of cells under S. aureus and E. coli treatment, and sheds new light on potential mechanisms and targets from the perspective of epigenetic modification in mastitis and other inflammatory diseases.
2022-02-23 | GSE196736 | GEO