The main sources of circulating cell-free DNA: Apoptosis, necrosis and active secretion

Hu, Zijian; Chen, Honghong; Long, Yanzhu; Li, Ping; Gu, Yueqing

doi:10.1016/j.critrevonc.2020.103166

Cited by 72 publications

(69 citation statements)

References 83 publications

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“…EMVs mediate intercellular communication and were shown to play essential roles in the pathogenesis of CRC, as they are implicated in tumorigenesis, CRC progression, chemotherapy resistance, and metastasis [ 55 , 56 ]. Details of individual cfNA types and their release mechanisms were comprehensively covered in previous works [ 57 , 58 , 59 , 60 , 61 ] and are not the focus [ 55 , 56 , 57 , 58 , 59 ] of this review.…”

Section: Cell-free Nucleic Acids As Crc Biomarkersmentioning

confidence: 99%

Extracellular Nucleic Acids in the Diagnosis and Progression of Colorectal Cancer

Styk

Buglyó

Pös

et al. 2022

Cancers

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Colorectal cancer (CRC) is the 3rd most common malignant neoplasm worldwide, with more than two million new cases diagnosed yearly. Despite increasing efforts in screening, many cases are still diagnosed at a late stage, when mortality is high. This paper briefly reviews known genetic causes of CRC (distinguishing between sporadic and familial forms) and discusses potential and confirmed nucleic acid biomarkers obtainable from liquid biopsies, classified by their molecular features, focusing on clinical relevance. We comment on advantageous aspects such as better patient compliance due to blood sampling being minimally invasive, the possibility to monitor mutation characteristics of sporadic and hereditary CRC in a disease showing genetic heterogeneity, and using up- or down-regulated circulating RNA markers to reveal metastasis or disease recurrence. Current difficulties and thoughts on some possible future directions are also discussed. We explore current evidence in the field pointing towards the introduction of personalized CRC management.

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Section: Cell-free Nucleic Acids As Crc Biomarkersmentioning

confidence: 99%

Extracellular Nucleic Acids in the Diagnosis and Progression of Colorectal Cancer

Styk

Buglyó

Pös

et al. 2022

Cancers

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“…If to consider their apoptosis as physiological suicide (i.e. holocrine Open Journal of Biophysics type of secretion), then cell-free DNA-primers [29] and TdT enzyme delivered in extracellular media can convert single extracellular deoxynucleotides into oligomers which are captured by neighboring cells, especially if they injured and needed in quick replenishment of exhausted pool of the phosphorylated precursors.…”

Section: Discussionmentioning

confidence: 99%

The Possible Involvement of Apoptotic Decay of Terminal Deoxynucleotidyl Transferase-Positive Lymphocytes in the Reutilization of the Extracellular DNA Fragments by Surrounding Living Cells

Shoutko¹

2021

OJBIPHY

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The migrating TdT + thymocytes can die in other tissues, promoting the surrounding cells' renewing likes holocrine secretion does. To clarify the role of TdT-enzyme for this function of progenitor lymphocytes, their extracellular media with its components included by living cells analyzed in vitro before and after in vivo irradiation of donor rats. The nucleoid with DNase-sensitive (free) DNA and TdT activity discovered in extracellular media conditioned preliminary by spontaneous apoptotic death of a minor part of the thymocyte's suspension in vitro. The penetration of labeled products of non-template synthesis with free DNA' primers from media into cells by pinocytosis confirmed by exogenous polymeric DNA marked artificially. The DNA penetration into cells follows an increase of the cell's viability and acceleration of spontaneous intracellular DNA-synthesis controlled with labeled thymidine uptake. Both phenomena are typical for either the lowest initial concentration of intact cells or their preliminary irradiation in vivo. The data point to possible involvement of apoptotic decay of TdT + cells in the reutilization of the extracellular DNA fragments for reparation/regeneration of surrounding living cells.

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“…C-cfDNA is widely used in clinical practice to confirm the diagnosis and prognosis of the disease and monitor the patient’s response to therapy. The main sources of circulating cell-free DNA are apoptosis, necrosis and active secretion [ 8 ]. The pool of c-cfDNA fragments can contain the DNA fragments of a tumor, fetus or transplanted organ, allowing fluid biopsy without traumatic intervention.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Analysis of Biological Activity of Circulating Cell-Free DNA Isolated from Blood Plasma of Schizophrenic Patients and Healthy Controls

Ershova

Shmarina

Porokhovnik

et al. 2022

Genes

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Schizophrenia is associated with low-grade systemic inflammation. Circulating cell-free DNA (c-cfDNA) belongs to the DAMP class. The major research question was: can the c-cfDNA of schizophrenic patients (sz-cfDNA) stimulate the DNA sensor genes, which control the innate immunity? We investigated the in vitro response of ten human skin fibroblast (HSF) lines to five DNA probes containing different amounts of a GC-rich marker (the ribosomal repeat) and a DNA oxidation marker (8-oxodG) including sz-cfDNA and healthy control c-cfDNA (hc-cfDNA) probes. After 1 h, 3 h, and 24 h of incubation, the expression of 6 protein genes responsible for cfDNA transport into the cell (EEA1 and HMGB1) and the recognition of cytosolic DNA (TLR9, AIM2, STING and RIG-I) was analyzed at the transcriptional (RT-qPCR) and protein level (flow cytometry and fluorescence microscopy). Additionally, we analyzed changes in the RNA amount of 32 genes (RT-qPCR), which had been previously associated with different cellular responses to cell-free DNA with different characteristics. Adding sz-cfDNA and hc-cfDNA to the HSF medium in equal amounts (50 ng/mL) blocked endocytosis and stimulated TLR9 and STING gene expression while blocking RIG-I and AIM2 expression. Sz-cfDNA and hc-cfDNA, compared to gDNA, demonstrated much stronger stimulated transcription of genes that control cell proliferation, cytokine synthesis, apoptosis, autophagy, and mitochondrial biogenesis. No significant difference was observed in the response of the cells to sz-cfDNA and hc-cfDNA. Sz-cfDNA and hc-cfDNA showed similarly high biological activity towards HSFs, stimulating the gene activity of TLR9 and STING DNA sensor proteins and blocking the activity of the AIM2 protein gene. Since the sz-cfDNA content in the patients’ blood is several times higher than the hc-cfDNA content, sz-cfDNA may upregulate pro-inflammatory cytokines in schizophrenia.

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The main sources of circulating cell-free DNA: Apoptosis, necrosis and active secretion

Cited by 72 publications

References 83 publications

Extracellular Nucleic Acids in the Diagnosis and Progression of Colorectal Cancer

Extracellular Nucleic Acids in the Diagnosis and Progression of Colorectal Cancer

The Possible Involvement of Apoptotic Decay of Terminal Deoxynucleotidyl Transferase-Positive Lymphocytes in the Reutilization of the Extracellular DNA Fragments by Surrounding Living Cells

In Vitro Analysis of Biological Activity of Circulating Cell-Free DNA Isolated from Blood Plasma of Schizophrenic Patients and Healthy Controls

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