Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 14, 2023; 29(30): 4642-4656
Published online Aug 14, 2023. doi: 10.3748/wjg.v29.i30.4642
Exploring the regulatory mechanism of tRNA-derived fragments 36 in acute pancreatitis based on small RNA sequencing and experiments
Xi-Rui Fan, Yun Huang, Yu Su, Si-Jin Chen, Yu-Lu Zhang, Wei-Kang Huang, Hui Wang
Xi-Rui Fan, Yun Huang, Yu Su, Si-Jin Chen, Yu-Lu Zhang, Wei-Kang Huang, Hui Wang, Department of Gastroenterology, The Affiliated Yan’an Hospital of Kunming Medical University, Kunming 650051, Yunnan Province, China
Xi-Rui Fan, Hui Wang, Key Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Yan’an Hospital of Kunming, Kunming 650051, Yunnan Province, China
Author contributions: Fan XR and Huang Y contributed equally to this work. Wang H conceived, designed, and supervised the study; Fan XR, Huang Y, and Chen SJ performed the majority of experiments and collected the data; Su Y and Huang WK performed data analysis and drafted the manuscript; and all authors have read and agreed to the published version of the manuscript.
Supported by the National Natural Science Foundation of China, No. 81860424.
Institutional review board statement: This study was approved by the Medical Ethics Committee of Yan’an Hospital Affiliated to Kunming Medical University (Approval No. 2022-024-01).
Institutional animal care and use committee statement: This study was approved by Animal Ethics and Welfare Committee (AEWC) of Kunming Yan’an hospital (Approval No. 2022013) in accordance with internationally accepted principles for the use of laboratory animals.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data used during the current study are available from the corresponding author on reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Hui Wang, PhD, Doctor, Department of Gastroenterology, The Affiliated Yan’an Hospital of Kunming Medical University, Renmin East Road, Panlong District, Kunming 650051, Yunnan Province, China.
Received: February 9, 2023
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
Processing time: 182 Days and 9.9 Hours

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.


To determine the regulatory mechanisms of tRNA-derived fragments (tRFs) in AP based on small RNA sequencing and experiments.


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.


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 ferroptosis-related 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 progression of AP by recruiting insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) to the p53 mRNA m6A modification site by binding to IGF2BP3, which enhanced p53 mRNA stability and promoted the ferroptosis of pancreatic follicle cells.


In conclusion, regulation of nuclear pre-mRNA domain-containing protein 1B promoted AP development by regulating the ferroptosis of pancreatic cells, thereby acting as a prospective therapeutic target for AP. In addition, this study provided a basis for understanding the regulatory mechanisms of tRFs in AP.

Keywords: Acute pancreatitis, tRNA-derived fragments, tRNA-derived fragments 36, Mouse models, Ferroptosis, Reverse transcription quantitative polymerase chain reaction

Core Tip: Based on reverse transcription quantitative polymerase chain reaction and bioinformatic analysis of small RNA sequencing data extracted from three patients and three healthy controls, and validated by 20 acute pancreatitis (AP) patients and 20 healthy controls, we found that tRNA-derived fragments 36 (tRF36) was significantly upregulated in AP. Furthermore, the results of the cell model of the MCP-83 cell line and knockdown of tRF36 suggested that tRF36 contributed to AP progression by promoting cell death.