A review on the crosstalk between non-coding RNAs and the cGAS-STING signaling pathway

In the innate immune system, the cyclic GMP-AMP synthase (cGAS)-interferon gene stimulator (STING) pathway activates the type I interferon (IFN) response and the NF-κB pathway by recognizing double-stranded DNAs, the imbalance of which plays a pivotal role in human diseases, including cancer, autoimmune and inflammatory diseases. Non-coding RNAs (ncRNAs) are a diverse group of transcripts that do not code for proteins but regulate various targets and signaling pathways in physiological and pathological processes. Recently, there has been increasing interest in investigating the interplay between the cGAS-STING pathway and ncRNAs. In this review, we provide a concise overview of the cGAS-STING pathway and ncRNAs. Then, we specifically delve into the regulation of the cGAS-STING pathway by long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), the three major classes of ncRNAs, and the influence of the cGAS-STING pathway on the expression of ncRNAs. Furthermore, we introduce the therapeutic applications targeting the cGAS-STING pathway and ncRNA therapy, and propose the utilization of drug delivery systems to deliver ncRNAs that influence the cGAS-STING pathway. Overall, this review highlights the emerging understanding of the intricate relationship between the cGAS-STING pathway and ncRNAs, shedding light on their potential as therapeutic targets in various diseases. •In this review, bidirectional interaction between the cGAS-STING pathway and non-coding RNAs (ncRNAs) is highlighted.•Regulation of the cGAS-STING pathway by long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs).•Influence of the cGAS-STING pathway on the expression of ncRNAs•Current application and limitations of cGAS-STING-pathway-targeted therapeutic approaches and potential synergies with ncRNAs