From Inflammatory RNAs to Therapeutic Silencing: Deciphering the RNA–Inflammation Axis in Cancer and Neurodegeneration

Inflammation is a critical protective response that maintains tissue homeostasis. However, persistent or dysregulated inflammation contributes significantly to the progression of cancer and neurodegenerative diseases. Recent advances in RNA biology have identified non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs, and circular RNAs, as key modulators of inflammatory signaling networks. These RNA molecules regulate key pathways such as NF-κB, STAT3, MAPK, and PI3K/AKT, thereby influencing immune responses, tumor progression, neuronal survival, and cellular stress adaptation. In parallel, RNA-sensing receptors, including Toll-like receptors and RIG-I-like receptors, connect innate immune activation with chronic inflammatory pathology. Emerging evidence further demonstrates that inflammatory RNAs participate in epigenetic regulation, intercellular communication, and inter-organ crosstalk through extracellular vesicles and exosomes. In cancer, RNA-mediated feedback loops sustain tumor-promoting inflammation, metastasis, and immune evasion, whereas in neurodegenerative disorders, they contribute to glial activation, neuronal dysfunction, and progressive neuroinflammation. This review examines the mechanistic relationship between RNA dysregulation and inflammation across cancer and neurodegeneration, with particular emphasis on RNA signaling networks, exosomal communication, and targeted RNA-based therapeutics. Collectively, advances in understanding the RNA–inflammation axis may reveal new opportunities for precision diagnostics and next generation therapeutic interventions.