From the Guidelines
Cytoplasmic DNA can have harmful effects on the body, particularly when it comes to viral infections like HBV, where integrated viral DNA can lead to genomic instability and cancer development.
Effects of Cytoplasmic DNA
- Genomic instability: HBV DNA integrations can facilitate chromosomal translocations, driving genomic instability and potentiate malignant transformation, as seen in hepatocellular carcinoma (HCC) development 1.
- Cancer development: HBV DNA insertional mutagenesis may result in the dysfunction of cancer-associated genes, such as telomerase reverse transcriptase (TERT), which is highly associated with cancer risk 1.
- Inflammatory response: Mitochondrial DNA (mtDNA) can act as a danger-associated molecular pattern, triggering an inflammatory response through the activation of toll-like receptor 9 (TLR9) and the NLRP3 inflammasome 1.
- Cell death: Fragmented mtDNA can lead to the activation of the NLRP3 inflammasome, inducing pyroptotic cell death, and mitochondrial dysfunction due to excessive oxidative stress can also elicit NLRP3 oligomerization 1.
Key Findings
- HBV DNA integrations are present in 80% of HCC tumors and can facilitate chromosomal translocations, driving genomic instability and cancer development 1.
- mtDNA can act as a danger-associated molecular pattern, triggering an inflammatory response and cell death 1.
- The inflammatory response plays a crucial role in the development and progression of diseases, such as ischemic stroke, and targeting the inflammatory response may offer a therapeutic approach 1.
From the Research
Effects of Cytoplasmic DNA on the Body
The presence of cytoplasmic DNA has been linked to various diseases, including inflammatory diseases and cancer. Some of the key effects of cytoplasmic DNA on the body include:
- Activation of immune responses, such as the production of type I interferons and the activation of inflammasomes 2, 3, 4
- Induction of cell death, including pyroptotic cell death, in response to cytoplasmic DNA 5, 4
- Contribution to the development of inflammatory diseases, such as rheumatoid arthritis and lung inflammatory diseases 2, 6
- Role in the pathogenesis of cancer, including lung carcinoma and myeloid leukemia 2, 5
Mechanisms of Cytoplasmic DNA Sensing
The mechanisms by which cytoplasmic DNA is sensed by the cell involve various proteins and pathways, including:
- STING (stimulator of interferon genes), which recognizes cytoplasmic DNA and activates downstream signaling pathways 3
- AIM2 (absent in melanoma 2), which senses cytoplasmic DNA and activates the inflammasome and cell death 4
- Autophagy, which regulates cytoplasmic DNA accumulation and subsequent redistribution into extracellular vesicles 5
Diseases Associated with Cytoplasmic DNA
Cytoplasmic DNA has been implicated in various diseases, including: