Evaluation of colorectal cancer in ulcerative colitis reveals key immune factors during its malignant transformation DOI Creative Commons

Jiao Ma,

Qing Wang, Chaoye Wang

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 18, 2023

Abstract BACKGROUND & AIMS: Ulcerative colitis (UC) is linked to an increased risk of colitis-associated colorectal cancer (CAC), which accounts for approximately 15% UC-related deaths. Despite this significant impact on patients, the mechanism behind how UC promotes development remains unknown. The present study aims investigate alterations in immune microenvironment during malignant transformation UC, shedding light underlying mechanisms carcinogenesis. METHODS We collected single-cell transcriptome samples 41 healthy samples, 45 and 148 cancer(CRC) from public databases. Using UC-CRC signature, we were able screen CAC-like samples. Based those datasets, several bioinformatics analyses performed 228,538 cells evaluate CAC. RESULTS predefined screened 14 revealed remodeling process tissue particularly involving VEGFA_Macro Treg cells. was significantly enriched showed a phenotype alteration disease progression, expressed more inflammation-related genes signal pathways. Additionally, proportion gradually with potentially promoting immunosuppressive microenvironment. Comparative analysis between sporadic CRC(sCRC) higher levels myeloid but reduced CD8 + T Finally, simplified signature ease clinical use screening CONCLUSIONS Our results may help improve understanding dynamic change CAC provide clues further exploration strategies prevent carcinogenesis UC.

Language: Английский

Matrix metalloproteinases as biomarkers and therapeutic targets in colitis-associated cancer DOI Creative Commons
Natalia Sampaio Moura, Alyssa Schledwitz, Madeline Alizadeh

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 13

Published: Jan. 15, 2024

Colorectal cancer (CRC) remains a major cause of morbidity and mortality. Therapeutic approaches for advanced CRC are limited rarely provide long-term benefit. Enzymes comprising the 24-member matrix metalloproteinase (MMP) family zinc- calcium-dependent endopeptidases key players in extracellular degradation, requirement colon tumor expansion, invasion, metastasis; hence, MMPs an important research focus. Compared to sporadic CRC, less is known regarding molecular mechanisms role development progression colitis-associated (CAC) − on background chronic inflammatory bowel disease (IBD) primarily ulcerative colitis Crohn’s disease. Hence, potential as biomarkers therapeutic targets CAC uncertain. Our goal was review data CAC. We sought identify promising prognostic opportunities novel lines investigation. A observation that since may be more active early phases CAC, using advancing neoplasia adjuvant therapy those with stage primary rather than overt metastases yield favorable outcomes.

Language: Английский

Citations

10
RNA Expression of MMP12 Is Strongly Associated with Inflammatory Bowel Disease and Is Regulated by Metabolic Pathways in RAW 264.7 Macrophages DOI Open Access
Laura Arosa, Miguel Camba-Gómez, L. Francisco Lorenzo‐Martín

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3167 - 3167

Published: March 9, 2024

Macrophage metalloelastase or matrix metalloproteinase-12 (MMP12) is a macrophage-specific proteolytic enzyme involved in the physiopathology of many inflammatory diseases, including bowel disease. Although previously published data suggested that modulation MMP12 macrophages could be determinant for development intestinal inflammation, scarce information available on mechanisms underlying regulation expression those phagocytes. Therefore, this study, we aimed to delineate association with disease and molecular events leading transcriptional control metalloproteinase. For that, used publicly data. Also, worked RAW 264.7 macrophage cell line functional experiments. Our results showed strong severity response relevant biological therapies. In vitro assays revealed inhibition mechanistic target rapamycin complex 1 (mTORC1) stimulation AMP-activated protein kinase (AMPK) signaling pathway potentiated Mmp12. Additionally, AMPK mTOR required downstream glycolytic fully engage Mmp12 expression. Finally, pharmacological abolished proinflammatory cytokine Interleukin-6 (Il6) macrophages. Overall, our findings provide better understanding its relationship inflammation.

Language: Английский

Citations

4
Selected Cytokines and Metalloproteinases in Inflammatory Bowel Disease DOI Open Access
Barbara Sosna, David Aebisher, Angelika Myśliwiec

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 25(1), P. 202 - 202

Published: Dec. 22, 2023

Inflammatory bowel disease (IBD) is a collective term for two diseases: ulcerative colitis (UC) and Crohn’s (CD). There are many factors, e.g., genetic, environmental immunological, that increase the likelihood of these diseases. Indicators IBDs include extracellular matrix metalloproteinases (MMPs). The aim this review to present data on role selected cytokines in IBD. In recent years, more transcriptomic studies emerging. These improving characterization cytokine microenvironment inside inflamed tissue. It observed levels several consistently increased tissue IBD, both UC CD. This shows MMPs play major pathology inflammatory processes, cancer, IBD-associated inflammation associated with expression reduced ability inhibitors (TIMPs) inhibit their action. IBD patients tissues inflamed, produced excess TIMP activity not sufficient block MMPs. based our personal selection literature was retrieved by selective search PubMed using terms “Inflammatory disease” “pathogenesis diseases” includes systematic reviews, meta-analyses, clinical trials. involvement immune system pathophysiology reviewed involved.

Language: Английский

Citations

7
MAD2L2 overexpression attenuates the effects of TNF-α-induced migration and invasion capabilities in colorectal cancer cells DOI Open Access
Haotong Sun,

HEYING WANG,

YANJIE HAO

et al.

Biocell, Journal Year: 2024, Volume and Issue: 48(9), P. 1311 - 1322

Published: Jan. 1, 2024

Background: Colorectal cancer is a major global health concern, exacerbated by tumor necrosis factor-alpha (TNF-α) and its role in inflammation, with the effects of Mitotic Arrest Deficient 2 Like (MAD2L2) this context still unclear.Methods: The colorectal carcinoma cell lines HCT116 SW620 were exposed to TNF-α for period 24 h instigate an inflammatory response.Subsequent assessments conducted measure expression cytokines, activity within p38 mitogen-activated protein kinase (p38 MAPK) Phosphoinositide 3-Kinase/AKT Serine/Threonine Kinase pathway (PI3K/AKT) signaling cascades.Transcriptome sequencing subsequent integrative analysis Cancer Genome Atlas (TCGA) program database revealed significant downregulation key factor MAD2L2.Enhancement MAD2L2 was facilitated via lentiviral vector-mediated transfection.The influence overexpression on TNF-α-prompted intracellular pathways, migratory invasive behaviors cells then scrutinized.Results: treatment significantly increased Interleukin-1 beta (IL-1β) Interleukin-6 (IL-6), activated MAPK PI3K/AKT enhanced migration invasion.A decrease observed following treatment.However, reversed TNF-α, reducing IL-1β IL-6 levels, attenuating activation, inhibiting invasion.Conclusions:Overexpression attenuates pro-inflammatory suggesting that plays protective against TNF-α-induced invasion cells.Therefore, holds potential as therapeutic target cancer.

Language: Английский

Citations

0
Solving the Puzzle: Molecular Research in Inflammatory Bowel Diseases DOI Open Access
Susanne M. Krug

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13389 - 13389

Published: Aug. 29, 2023

Inflammatory bowel disease (IBD) encompasses chronic idiopathic relapsing and remitting gastrointestinal autoimmune diseases characterized by inflammatory disorders of complex etiology, posing clinical challenges due to their often therapy-refractory nature [...]

Language: Английский

Citations

0
Evaluation of colorectal cancer in ulcerative colitis reveals key immune factors during its malignant transformation DOI Creative Commons

Jiao Ma,

Qing Wang, Chaoye Wang

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 18, 2023

Abstract BACKGROUND & AIMS: Ulcerative colitis (UC) is linked to an increased risk of colitis-associated colorectal cancer (CAC), which accounts for approximately 15% UC-related deaths. Despite this significant impact on patients, the mechanism behind how UC promotes development remains unknown. The present study aims investigate alterations in immune microenvironment during malignant transformation UC, shedding light underlying mechanisms carcinogenesis. METHODS We collected single-cell transcriptome samples 41 healthy samples, 45 and 148 cancer(CRC) from public databases. Using UC-CRC signature, we were able screen CAC-like samples. Based those datasets, several bioinformatics analyses performed 228,538 cells evaluate CAC. RESULTS predefined screened 14 revealed remodeling process tissue particularly involving VEGFA_Macro Treg cells. was significantly enriched showed a phenotype alteration disease progression, expressed more inflammation-related genes signal pathways. Additionally, proportion gradually with potentially promoting immunosuppressive microenvironment. Comparative analysis between sporadic CRC(sCRC) higher levels myeloid but reduced CD8 + T Finally, simplified signature ease clinical use screening CONCLUSIONS Our results may help improve understanding dynamic change CAC provide clues further exploration strategies prevent carcinogenesis UC.

Language: Английский

Citations

0