# Unveiling the Role of circRNAs in Pyroptotic Signalling: From Molecular Crosstalk to Disease Modulation

## TL;DR

This review explores how circular RNAs (circRNAs) regulate pyroptosis, a type of cell death linked to inflammation and disease, and their potential for clinical applications.

## Contribution

The paper systematically summarizes the mechanisms and roles of circRNAs in pyroptosis across different pathways and diseases.

## Key findings

- CircRNAs regulate pyroptosis by acting as miRNA sponges, modulating protein activity, and encoding polypeptides.
- They play significant roles in canonical, noncanonical, and caspase-3/8-mediated pyroptosis pathways.
- CircRNAs are implicated in disease progression and offer potential for diagnostic and therapeutic strategies.

## Abstract

Pyroptosis is a gasdermins‐dependent programmed cell death (PCD) characterised by progressive cellular swelling and plasma membrane rupture (PMR). This process releases intracellular contents that amplify inflammatory cascades and immune activation, involving the pathogenesis of various disorders such as tumours, heart and vascular diseases, diabetic complications and inflammatory/infectious disorders. With the advancement of research, the regulatory role of noncoding RNA (ncRNA) in the pyroptosis pathway was delineated. Among, studies have demonstrated that circular RNAs (circRNAs) regulate the pyroptosis cascade mainly through three principal mechanisms: functioning as miRNA sponges, modulating protein activity and encoding functional polypeptides. Numerous circRNAs regulating pyroptosis have been characterised, indicating their significant role in this process and associated disease progression. This review systematically summarised current knowledge on the regulatory mechanisms of circRNAs in canonical, noncanonical and caspase‐3/8‐mediated pyroptosis pathways. We further discussed their pathophysiological roles in disease development and potential clinical applications, aiming to advance mechanistic understanding, facilitate clinical translation and inform diagnostic and therapeutic strategies.