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Non-coding RNA-Mediated Regulation of the cGAS-STING Pathway in Tumor Immunology: A Systematic Review
Mehran Molavand1,2, Mahdi Akbari Soufiani1,2, Amir Valizadeh1,2
1Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Current Medicinal Chemistry
|June 1, 2026
Summary
Non-coding RNAs (ncRNAs) have a dual role in cancer immunity, either enhancing anti-tumor responses by activating the cGAS-STING pathway or suppressing immunity and driving resistance. Further research is needed to clarify their mechanisms and therapeutic potential.
Area of Science:
- Immunology
- Molecular Biology
- Cancer Research
Background:
- The cGAS-STING pathway is crucial for innate immune sensing of cytosolic DNA and anti-tumor responses.
- Non-coding RNAs (ncRNAs), including miRNAs, circRNAs, and lncRNAs, are increasingly recognized as regulators of the cGAS-STING pathway within the tumor microenvironment.
Purpose of the Study:
- To systematically review and evaluate how ncRNAs modulate the cGAS-STING pathway.
- To assess the effects of ncRNA-mediated cGAS-STING regulation on anti-tumor immunity.
Main Methods:
- A systematic literature search was conducted across major databases (PubMed, EMBASE, Web of Science, Scopus) up to August 9, 2025.
- Inclusion criteria focused on in vitro and in vivo studies examining ncRNA regulation of cGAS-STING in cancer.
- Data were extracted and qualitatively synthesized following PRISMA guidelines.
Main Results:
- Eighteen studies were included, revealing diverse and sometimes contradictory findings regarding ncRNA-cGAS-STING interactions.
- Eight studies indicated ncRNAs enhance anti-tumor immunity via cGAS-STING activation, while two reported inhibitory effects.
- ncRNA modulation of cGAS-STING was linked to radiosensitivity, drug resistance, poorer outcomes, and treatment toxicities.
Conclusions:
- ncRNAs exhibit a context-dependent, dual role in regulating the cGAS-STING pathway, capable of potentiating anti-tumor immunity or suppressing signaling and driving resistance.
- The complexity of ncRNA function highlights their potential as biomarkers and therapeutic targets.
- Further research is essential to elucidate mechanisms, define conditions for activation versus suppression, and validate findings in preclinical and clinical models.
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