Published online Aug 14, 2023. doi: 10.3748/wjg.v29.i30.4642
Peer-review started: February 9, 2023
First decision: May 16, 2023
Revised: May 26, 2023
Accepted: July 17, 2023
Article in press: July 17, 2023
Published online: August 14, 2023
Acute pancreatitis (AP), also known as acute inflammation of the pancreas, is an inflammatory injury resulting from the activation of pancreatic enzymes caused by a variety of pathogenic factors, leading to self-digestion of pancreatic tissue.
Difficult treatment, high morbidity, many complications, high cost, and poor prognosis are the current clinical status. Therefore, it is particularly important to investigate the pathogenesis of AP.
Screening for tRNA-derived fragments (tRFs) contribute to AP progression and exploring the molecular mechanism of its action were the main objectives of our study.
Firstly, key tRFs and the potential mechanisms of action were explored based on the small RNA sequencing and functional enrichment analyses in AP. The role of tRF36 was investigated by constructing the AP cell and mouse models. Subsequently, the lipase, amylase, and cytokine levels were assayed to examine AP progression. Evaluation of cellular ferroptosis was implemented by analyzing the ferritin expression, reactive oxygen species, malondialdehyde, and ferric ion levels. Finally, RNA pull down assays and methylated RNA immunoprecipitation were performed to explore the molecular mechanisms.
In total, 211 differentially expressed tRFs including 116 upregulated and 95 downregulated were identified. According to reverse transcription quantitative polymerase chain reaction, tRF36 was significantly upregulated in the serum of AP patients, compared to healthy controls. Moreover, the occurrence of pancreatic cell ferroptosis was detected in AP cells and mouse models. Furthermore, we hypothesized that tRF36 accelerated AP progression by binding to insulin-like growth factor 2 mRNA binding protein 3, which was recruited to the p53 mRNA m6A modification site, thereby enhancing the stability of p53 mRNA and promoting ferroptosis in pancreatic follicular cells.
tRF36 promoted AP development by regulating the ferroptosis of pancreatic cells, which would provide a new theoretical basis for understanding the regulatory mechanism of tRF in AP, and also provide new targets for the treatment of AP.
We will further validate the results of this study and continue to monitor the role of tRF36 in the development process of AP.