Abstract
tRNA-derived small RNAs (tsRNAs), encompassing tRNA fragments (tRFs) and tRNA-derived stress-induced RNAs (tiRNAs), represent a category of non-coding small RNAs (sncRNAs) that are increasingly recognized for their diverse biological functions. These functions include gene silencing, ribosome biogenesis, retrotransposition, and epigenetics. tsRNAs have been identified as key players in the progression of various tumors, yet their specific roles in pancreatic cancer (PC) and acute pancreatitis (AP) remain largely unexplored. Pancreatic cancer, particularly pancreatic ductal adenocarcinoma, is notorious for its high mortality rate and extremely low patient survival rate, primarily due to challenges in early diagnosis. Similarly, acute pancreatitis is a complex and significant disease. This article reviews the roles of 18 tsRNAs in PC and AP, focusing on their mechanisms of action and potential clinical applications in these two diseases. These tsRNAs influence the progression of pancreatic cancer and acute pancreatitis by modulating various pathways, including ZBP1/NLRP3, Hippo, PI3K/AKT, glycolysis/gluconeogenesis, and Wnt signaling. Notably, the dysregulation of tsRNAs is closely linked to critical clinical factors in pancreatic cancer and acute pancreatitis, such as lymph node metastasis, tumor-node-metastasis (TNM) stage, overall survival (OS), and disease-free survival (DFS). This article not only elucidates the mechanisms by which tsRNAs affect pancreatic cancer and acute pancreatitis but also explores their potential as biomarkers and therapeutic targets for pancreatic cancer. The insights provided here offer valuable references for future research, highlighting the importance of tsRNAs in the diagnosis and treatment of these challenging diseases.