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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
PubMed
Abstract

Insights

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.
Keywords:
Anti-tumor immunity.DNA sensingInnate immunitycGAS-STING pathwaycircRNAslncRNAsmiRNAs

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