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
Research background

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.

Research motivation

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.

Research objectives

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.

Research methods

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.

Research results

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.

Research conclusions

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.

Research perspectives

We will further validate the results of this study and continue to monitor the role of tRF36 in the development process of AP.