Targeting the non-coding RNA-PANoptosis axis: a novel frontier in disease diagnosis and therapy

Programmed cell death represents a fundamental process in maintaining organismal homeostasis and responding to pathological challenges. The traditional view considered apoptosis, pyroptosis, and necroptosis as independent death pathways. However, recent research has revealed extensive interactions and synergies among these pathways, leading to the emergence of a novel form of cell death termed "PANoptosis." Triggered by specific stimuli, PANoptosis involves the assembly of a large multiprotein complex called the PANoptosome. This complex integrates key molecules and morphological features from apoptosis, pyroptosis, and necroptosis, culminating in a highly efficient and coordinated inflammatory cell death program. Concurrently, non-coding RNAs, as crucial regulators of gene expression, participate extensively in the regulation of cellular fate at the post-transcriptional and epigenetic levels. This review systematically summarizes the molecular mechanisms by which non-coding RNAs regulate the core components of PANoptosis and its upstream signaling pathways. It further delves into the pathological role of this regulatory axis in infectious diseases, cancer, neurodegenerative disorders, and autoimmune diseases. Additionally, the article explores the diagnostic potential of non-coding RNA-based approaches and therapeutic strategies targeting the non-coding RNA-PANoptosis axis, while also addressing current challenges related to mechanistic complexity, delivery technologies, and safety assessment. This review aims to establish a systematic framework for the "non-coding RNA-PANoptosis-disease" regulatory axis, providing a theoretical basis for understanding the interactive logic of cell death networks and for developing precise interventions for related diseases.