Tehran University of Medical Sciences Acta Biochimica Iranica 0001-5261 3 4 2025 12 22 206 214 Jamal Amri 1. Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Mohammad Reza Zarei 1. Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Elham Esmaeilzadeh Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Reza Meshkani 1. Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 2026 01 01 2026 02 05 The cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS–STING) signaling pathway is a central component of innate immunity that senses cytosolic double‑stranded DNA and initiates type I interferon and inflammatory responses. Controlled activation of this pathway is essential for antimicrobial defense and antitumor immune surveillance. In contrast, dysregulated or persistent signaling can promote chronic inflammation, tissue damage, autoimmune disorders, or immune evasion in cancer and infectious diseases. Therefore, tight regulation of cGAS–STING activity is critical for maintaining immune homeostasis. MicroRNAs (miRNAs) have emerged as key post‑transcriptional regulators that fine‑tune cGAS–STING signaling by directly targeting core pathway components or indirectly modulating related immune signaling molecules. This article provides a comprehensive review of current evidence describing miRNA‑mediated regulation of the cGAS–STING axis across diverse pathological contexts, including malignancies, viral and bacterial infections, and autoimmune or inflammatory diseases. In various cancers, miRNA‑mediated suppression of this pathway contributes to reduced interferon signaling, immune escape, therapy resistance, and tumor progression, although in certain cellular settings, controlled inhibition of cGAS–STING may exert protective or antitumor effects. During infectious diseases, some miRNAs are exploited by pathogens to attenuate innate immune sensing, whereas others enhance host defense by modulating negative regulators of immune signaling. In autoimmune and inflammatory disorders, dysregulated miRNA expression can either restrain excessive inflammation or exacerbate disease progression. Overall, this review underscores the miRNA–cGAS–STING regulatory axis as a dynamic and context‑specific network with broad relevance across human diseases. https://abi.tums.ac.ir/index.php/abi/article/view/175 https://abi.tums.ac.ir/index.php/abi/article/download/175/121