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. 2022 Feb;13(2):3207-3220.
doi: 10.1080/21655979.2021.2018880.

Effects of tRNA-derived fragments and microRNAs regulatory network on pancreatic acinar intracellular trypsinogen activation

Hao Yang  1 , Huairong Zhang  2 , Zhuomiaoyu Chen  3 , Yuan Wang  3 , Bo Gao  3
Affiliations

Effects of tRNA-derived fragments and microRNAs regulatory network on pancreatic acinar intracellular trypsinogen activation

Hao Yang et al. Bioengineered. 2022 Feb.

Abstract

Acute pancreatitis (AP) is a common gastrointestinal disease with substantial morbidity and mortality. Pancreatic acinar intracellular trypsinogen activation (PAITA) is an important event in the early stage of AP. The present study aimed to investigate the effects of tRNA-derived fragments (tRFs) and the microRNA regulatory network on pancreatic acinar intracellular trypsinogen activation (PAITA) and identify novel key targets in AP. Taurolithocholic acid 3-sulfate (TLC-S)-treated AR42J cells were used to establish a PAITA model. Twenty differentially expressed tRFs and 35 DE microRNAs were identified in PAITA through gene sequencing. Based on these genes, we established the tRF-mRNA and microRNA-mRNA regulatory networks by using bioinformatics methods. The networks revealed 29 hub microRNAs (e.g., Let-7 family, miR-21-3p.) and 19 hub tRFs (e.g., tRF3-Thr-AGT, i-tRF-Met-CAT) in PAITA. GO analysis showed that the functions of the two networks were similar and mainly enriched in RNA splicing, mRNA processing, and so on. tRF3-Thr-AGT, targeting Btg2, Cd44, Zbp1, etc., was significantly decreased in PAITA. Moreover, the trypsinogen activation level was increased significantly in the tRF3-Thr-AGT deficiency groups, but rescued by tRF3-Thr-AGT mimics. The results revealed that downregulated tRF3-Thr-AGT was involved in PAITA. This study provides potential novel targets for researching the underlying mechanisms of AP.

Keywords: Acute pancreatitis; small non-coding RNA; tRF3-THr-AGT; tRNA-derived fragments; trypsinogen activation.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
The heatmap of DE microRNA, tRF/tiRNA and mRNA.
Figure 2.
Figure 2.
The microRNA-mRNA regulatory network in PAITA. Triangle represents microRNA. Circle represents mRNA. Circle with gray edge represents transcription factor. Color represents the p value of DE genes. Node size represents network degree of DE gene.
Figure 3.
Figure 3.
The tRF/tiRNA-mRNA regulatory network in PAITA. Triangle represents tRF/tiRNA. Circle represents mRNA. Circle with gray edge represents transcription factor. Color represents the p value of DE genes. Node size represents network degree of DE gene.
Figure 4.
Figure 4.
GO and KEGG pathway analysis of the microRNA-mRNA regulatory network in PAITA.
Figure 5.
Figure 5.
GO and KEGG pathway analysis of the tRF/tiRNA-mRNA regulatory network in PAITA.
Figure 6.
Figure 6.
Combined microRNA and tRF/tiRNA regulatory network in PAITA.
Figure 7.
Figure 7.
The distribution of six tRF/tiRNA types in PAITA. a, Overall distribution of six tRF/tiRNA types. b, Distribution of six tRF/tiRNA types in each tRNA.
Figure 8.
Figure 8.
The expression of tRF3-Thr-AGT in PAITA and RNA intervention. a, The fold change of tRF3-Thr-AGT in PAITA. b, The sequence and location of tRF3-Thr-AGT in tRNA. c, Verification of tRF3-Thr-AGT source. d, The expression of tRF3-Thr-AGT in each group after RNA intervention. ***P < 0.001.
Figure 9.
Figure 9.
Trypsinogen activation in each group after RNA intervention. a, Image fromlaser confocal microscopy. b, Histogram of flow cytometry. c, Chart of statistics. **P < 0.01. ***P < 0.001.
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Publication types

Grants and funding

NationalNatural Science Foundation of China, Grant number: 81800573; Peking University People’s Hospital Research and Development Funds, Grant number: Peking University People’s Hospital Research and Development Funds RDY201806.