Exploring the regulatory mechanism of tRNA-derived fragments 36 in acute pancreatitis based on small RNA sequencing and experiments  

作　　者：Xi-Rui Fan Yun Huang Yu Su Si-Jin Chen Yu-Lu Zhang Wei-Kang Huang Hui Wang 

机构地区：[1]Department of Gastroenterology,The Affiliated Yan’an Hospital of Kunming Medical University,Kunming 650051,Yunnan Province,China [2]Key Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province,Yan’an Hospital of Kunming,Kunming 650051,Yunnan Province,China

出　　处：《World Journal of Gastroenterology》2023年第30期4642-4656,共15页世界胃肠病学杂志（英文版）

基　　金：the National Natural Science Foundation of China,No.81860424.

摘　　要：BACKGROUND Acute pancreatitis(AP)is a disease featuring acute inflammation of the pancreas and histological destruction of acinar cells.Approximately 20%of AP patients progress to moderately severe or severe pancreatitis,with a case fatality rate of up to 30%.However,a single indicator that can serve as the gold standard for prognostic prediction has not been discovered.Therefore,gaining deeper insights into the underlying mechanism of AP progression and the evolution of the disease and exploring effective biomarkers are important for early diagnosis,progression evaluation,and precise treatment of AP.AIM To determine the regulatory mechanisms of tRNA-derived fragments(tRFs)in AP based on small RNA sequencing and experiments.METHODS Small RNA sequencing and functional enrichment analyses were performed to identify key tRFs and the potential mechanisms in AP.Reverse transcription quantitative polymerase chain reaction(RT-qPCR)was conducted to determine tRF expression.AP cell and mouse models were created to investigate the role of tRF36 in AP progression.Lipase,amylase,and cytokine levels were assayed to examine AP progression.Ferritin expression,reactive oxygen species,malondialdehyde,and ferric ion levels were assayed to evaluate cellular ferroptosis.RNA pull down assays and methylated RNA immunoprecipitation were performed to explore the molecular mechanisms.RESULTS RT-qPCR results showed that tRF36 was significantly upregulated in the serum of AP patients,compared to healthy controls.Functional enrichment analysis indicated that target genes of tRF36 were involved in ferroptosisrelated pathways,including the Hippo signaling pathway and ion transport.Moreover,the occurrence of pancreatic cell ferroptosis was detected in AP cells and mouse models.The results of interference experiments and AP cell models suggested that tRF-36 could promote AP progression through the regulation of ferroptosis.Furthermore,ferroptosis gene microarray,database prediction,and immunoprecipitation suggested that tRF-36 accelerated the p

关 键 词：Acute pancreatitis tRNA-derived fragments tRNA-derived fragments 36 Mouse models Ferroptosis Reverse transcription quantitative polymerase chain reaction 

分 类 号：R576[医药卫生—消化系统]