MicroRNAs and cGAS-STING Axis: Modulating Innate Immunity in Pathophysiological Contexts

Abstract

The cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS–STING)signaling pathway is a central component of innate immunity that senses cytosolicdouble stranded DNA and initiates type I interferon and inflammatory responses.Controlled activation of this pathway is essential for antimicrobial defense and antitumorimmune surveillance. In contrast, dysregulated or persistent signaling can promotechronic inflammation, tissue damage, autoimmune disorders, or immune evasion incancer and infectious diseases. Therefore, tight regulation of cGAS–STING activity iscritical for maintaining immune homeostasis. MicroRNAs (miRNAs) have emerged askey post transcriptional regulators that fine tune cGAS–STING signaling by directlytargeting core pathway components or indirectly modulating related immune signalingmolecules. This article provides a comprehensive review of current evidence describingmiRNA mediated regulation of the cGAS–STING axis across diverse pathologicalcontexts, including malignancies, viral and bacterial infections, and autoimmuneor inflammatory diseases. In various cancers, miRNA mediated suppression of thispathway contributes to reduced interferon signaling, immune escape, therapy resistance,and tumor progression, although in certain cellular settings, controlled inhibition ofcGAS–STING may exert protective or antitumor effects. During infectious diseases,some miRNAs are exploited by pathogens to attenuate innate immune sensing, whereasothers enhance host defense by modulating negative regulators of immune signaling. Inautoimmune and inflammatory disorders, dysregulated miRNA expression can eitherrestrain excessive inflammation or exacerbate disease progression. Overall, this reviewunderscores the miRNA–cGAS–STING regulatory axis as a dynamic and contextspecific network with broad relevance across human diseases