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Cellular Heterogeneity and IL-17 Pathway Dynamics Reveal Insights into the Transition from Ulcerative Colitis to Colorectal Cancer Through scRNA-Seq Analysis.

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Názov: Cellular Heterogeneity and IL-17 Pathway Dynamics Reveal Insights into the Transition from Ulcerative Colitis to Colorectal Cancer Through scRNA-Seq Analysis.
Autori: Li, Yaxian, Sun, Ruochuan, Wang, Xiaodong, Ma, Mengdi, Wang, Huizhen, Yang, Bo, Lu, Yida, Li, Yongxiang
Zdroj: Journal of Inflammation Research; May2025, Vol. 18, p6927-6944, 18p
Predmety: EPITHELIAL cells, METABOLIC reprogramming, REGULATORY T cells, T cells, ULCERATIVE colitis
Abstrakt: Introduction: The progression of UC to CACRC involves substantial molecular and cellular alterations. A deeper understanding of these changes is essential for identifying potential therapeutic targets and improving disease outcomes. Methods: We performed scRNA-seq on tissue samples from a patient with coexisting UC and CACRC lesions, including normal colon, UC-affected tissue, and CACRC. Cell clustering, differential gene expression, and KEGG pathway enrichment analyses were conducted to characterize cellular heterogeneity and pathway dynamics. Results: Thirteen distinct cell clusters were identified, reflecting significant heterogeneity across disease stages. Six major cell types—B cells, T cells, epithelial cells, monocytes, neutrophils, and CMPs—were selected for in-depth analysis. Epithelial cells from UC samples showed marked upregulation of inflammatory genes such as IL-17A, CXCL1, IL-6, MMP3, and TNFAIP3, which were downregulated in CACRC. KEGG analysis revealed IL-17 signaling as a key pathway involved in disease progression. A progressive increase in Tregs, supported by elevated CD25 expression, was observed from normal tissue through UC to CACRC. Furthermore, C-MYC was significantly upregulated in CACRC epithelial cells, suggesting its role in tumor proliferation and metabolic reprogramming. Conclusion: This study uncovers dynamic cellular and molecular changes during the transition from UC to CACRC, highlighting IL-17 signaling, Treg expansion, and C-MYC activation as potential drivers of malignancy and targets for future therapeutic intervention. [ABSTRACT FROM AUTHOR]
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Databáza: Biomedical Index
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Abstrakt:Introduction: The progression of UC to CACRC involves substantial molecular and cellular alterations. A deeper understanding of these changes is essential for identifying potential therapeutic targets and improving disease outcomes. Methods: We performed scRNA-seq on tissue samples from a patient with coexisting UC and CACRC lesions, including normal colon, UC-affected tissue, and CACRC. Cell clustering, differential gene expression, and KEGG pathway enrichment analyses were conducted to characterize cellular heterogeneity and pathway dynamics. Results: Thirteen distinct cell clusters were identified, reflecting significant heterogeneity across disease stages. Six major cell types—B cells, T cells, epithelial cells, monocytes, neutrophils, and CMPs—were selected for in-depth analysis. Epithelial cells from UC samples showed marked upregulation of inflammatory genes such as IL-17A, CXCL1, IL-6, MMP3, and TNFAIP3, which were downregulated in CACRC. KEGG analysis revealed IL-17 signaling as a key pathway involved in disease progression. A progressive increase in Tregs, supported by elevated CD25 expression, was observed from normal tissue through UC to CACRC. Furthermore, C-MYC was significantly upregulated in CACRC epithelial cells, suggesting its role in tumor proliferation and metabolic reprogramming. Conclusion: This study uncovers dynamic cellular and molecular changes during the transition from UC to CACRC, highlighting IL-17 signaling, Treg expansion, and C-MYC activation as potential drivers of malignancy and targets for future therapeutic intervention. [ABSTRACT FROM AUTHOR]
ISSN:11787031
DOI:10.2147/JIR.S505313