Non-coding RNAs in pancreatitis: from mechanisms to therapeutics

Pancreatitis is a complex inflammatory condition of the pancreas and can be classified into acute pancreatitis (AP) and chronic pancreatitis (CP). The pathogenesis of the disease remains unclear, and effective preventive or therapeutic strategies are currently lacking. Non-coding RNA (ncRNA) regulatory networks consist primarily of miRNAs, lncRNAs, and circRNAs, which precisely regulate gene expression through complex interactions and play a key role in fibrosis and inflammation. In terms of AP, ncRNAs could modulate the activity of pancreatic acinar cells, autophagic flux, inflammatory cell infiltration and the integrity of the intestinal mucosal barrier, which regulates local pancreatic and systemic inflammation. During the progression of CP, ncRNAs mediate the pancreatic persistent inflammation and collagen deposition by regulating the interactions between pancreatic stellate cells and immune cells. ncRNAs serve as promising non-invasive biomarkers for pancreatitis, enabling early diagnosis, severity stratification, complication prediction and differential diagnosis between CP and pancreatic cancer. Therapeutically, ncRNAs represent potential precision intervention targets due to their high regulatability and specificity, although ncRNA-based therapies currently remain at the preclinical stage. Key challenges such as delivery efficiency and targeting specificity must be addressed to facilitate clinical translation. Overall, ncRNAs offer a novel avenue for improving the clinical management of pancreatitis.