Microsatellite Alterations in Free-Circulating Serum DNA in Patients with Ulcerative Colitis

Rauh, Peter; Rickes, Steffen; Fleischhacker, Michael

doi:10.1159/000075361

Cited by 14 publications

(12 citation statements)

References 19 publications

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“…In terms of their origin, cfDNAs fall into several categories. Endogenous cfDNA sequences are derived from tissues and cells, while exogenous ones are derived primarily from the host microbiome, infectious agents, fetus, and food [ 33 – 36 ].…”

Section: Discussionmentioning

confidence: 99%

Survival of HT29 cancer cells is influenced by hepatocyte growth factor receptor inhibition through modulation of self-DNA-triggered TLR9-dependent autophagy response

et al. 2022

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HGFR activation drives the malignant progression of colorectal cancer, and its inhibition displays anti-autophagic activity. The interrelated role of HGFR inhibition and TLR9/autophagy signaling in HT29 cancer cells subjected to modified self-DNA treatments has not been clarified. We analyzed this complex interplay with cell metabolism and proliferation measurements, TLR9, HGFR and autophagy inhibitory assays and WES Simple Western blot-based autophagy flux measurements, gene expression analyses, immunocytochemistry, and transmission electron microscopy. The overexpression of MyD88 and caspase-3 was associated with enhanced HT29 cell proliferation, suggesting that incubation with self-DNAs could suppress the apoptosis-induced compensatory cell proliferation. HGFR inhibition blocked the proliferation-reducing effect of genomic and hypermethylated, but not that of fragmented DNA. Lowest cell proliferation was achieved with the concomitant use of genomic DNA, HGFR inhibitor, and chloroquine, when the proliferation stimulating effect of STAT3 overexpression could be outweighed by the inhibitory effect of LC3B, indicating the putative involvement of HGFR-mTOR-ULK1 molecular cascade in HGFR inhibitor-mediated autophagy. The most intense cell proliferation was caused by the co-administration of hypermethylated DNA, TLR9 and HGFR inhibitors, when decreased expression of both canonical and non-canonical HGFR signaling pathways and autophagy-related genes was present. The observed ultrastructural changes also support the context-dependent role of HGFR inhibition and autophagy on cell survival and proliferation. Further investigation of the influence of the studied signaling pathways and cellular processes can provide a basis for novel, individualized anti-cancer therapies.

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Section: Discussionmentioning

confidence: 99%

Survival of HT29 cancer cells is influenced by hepatocyte growth factor receptor inhibition through modulation of self-DNA-triggered TLR9-dependent autophagy response

et al. 2022

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“…FcDNA in blood is originated from several sources [5,36,37]. Factors influencing fcDNA clearance include endogenous plasma nucleases, cell surface nucleases, their binding to receptors, and the subsequent intracellular degeneration [38][39][40].…”

Section: Discussionmentioning

confidence: 99%

“…Either amount of these sequences and their quality may be altered within chronic inflammatory disorders, such as systemic lupus erythematodes (SLE) or IBDs [5,6]. Furthermore, a close correlation between the quantity of fcDNA and the course or prognosis of several physiologic and pathologic conditions has been described [7].…”

Section: Introductionmentioning

confidence: 99%

Preconditioning with Intravenous Colitic Cell-Free DNA Prevents DSS-Colitis by Altering TLR9-Associated Gene Expression Profile

et al. 2014

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During the process of acute colitis, the subsequent inflammatory environment presumably results in changes of fcDNA with the potential to facilitate the downregulation of inflammation and improvement of regeneration. Thus, preconditioning of mice with colitis-derived fcDNA via TLR9 signaling could exert a tissue-protective effect and influence beneficially the course of DSS-colitis. Elucidating mechanisms of immune response alterations by nucleic acids may provide further insight into the etiology of IBD and develop the basis of novel immunotherapies.

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“…In 2003, Rauh et al showed for the first time that it is possible to detect cfDNA in the serum of UC patients, and that this cfDNA contained a microsatellite alteration previously identified in mucosa cells from UC patients [69]. A valuable study came from Koike et al, who detected a significantly higher amount of cfDNA in the circulation of mice with DSS-induced colitis compared to the control group.…”

Section: Cell-free Dna In Ibdmentioning

confidence: 99%

Cell-Free Nucleic Acids and their Emerging Role in the Pathogenesis and Clinical Management of Inflammatory Bowel Disease

Kubiritova

Radvánszky

Gardlík

2019

IJMS

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Cell-free nucleic acids (cfNAs) are defined as any nucleic acids that are present outside the cell. They represent valuable biomarkers in various diagnostic protocols such as prenatal diagnostics, the detection of cancer, and cardiovascular or autoimmune diseases. However, in the current literature, little is known about their implication in inflammatory bowel disease (IBD). IBD is a group of multifactorial, autoimmune, and debilitating diseases with increasing incidence worldwide. Despite extensive research, their etiology and exact pathogenesis is still unclear. Since cfNAs were observed in other autoimmune diseases and appear to be relevant in inflammatory processes, their role in the pathogenesis of IBD has also been suggested. This review provides a summary of knowledge from the available literature about cfDNA and cfRNA and the structures involving them such as exosomes and neutrophil extracellular traps and their association with IBD. Current studies showed the promise of cfNAs in the management of IBD not only as biomarkers distinguishing patients from healthy people and differentiating active from inactive disease state, but also as a potential therapeutic target. However, the detailed biological characteristics of cfNAs need to be fully elucidated in future experimental and clinical studies.

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Microsatellite Alterations in Free-Circulating Serum DNA in Patients with Ulcerative Colitis

Cited by 14 publications

References 19 publications

Survival of HT29 cancer cells is influenced by hepatocyte growth factor receptor inhibition through modulation of self-DNA-triggered TLR9-dependent autophagy response

Survival of HT29 cancer cells is influenced by hepatocyte growth factor receptor inhibition through modulation of self-DNA-triggered TLR9-dependent autophagy response

Preconditioning with Intravenous Colitic Cell-Free DNA Prevents DSS-Colitis by Altering TLR9-Associated Gene Expression Profile

Cell-Free Nucleic Acids and their Emerging Role in the Pathogenesis and Clinical Management of Inflammatory Bowel Disease

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