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A novel function of IRF9 in acute pancreatitis by modulating cell apoptosis, proliferation, migration, and suppressing SIRT1-p53

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Abstract

Acute pancreatitis (AP) is an inflammatory disease caused by the abnormal activation of pancreatic enzymes in the pancreas, with a considerably high morbidity and mortality. However, the etiological factor and pathogenesis of AP are still unclear. This study was aimed to explore the role and mechanism of interferon regulatory factor 9 (IRF9) in the occurrence of AP and to provide experimental and theoretical foundation for AP diagnosis and treatment. AP model in vitro was established by caerulein-induced group. Small interfering RNA (siRNA) was designed and constructed to silence IRF9 gene. After siRNA transfected and caerulein treated successfully, the expression levels of IRF9, SIRT1, and acetylated p53 (Ac-p53) were determined by qRT-PCR and Western blot. The apoptosis, proliferation, and migration of AR42J cells were checked by flow cytometry, MTT, and transwell assay. Dual-luciferase reporter assay was implemented to validate the regulatory effect of IRF9 on SIRT1. Here, our study showed that the expression of IRF9 and Ac-p53 was increased, SIRT1 was decreased, and cell apoptosis, proliferation, and migration of AR42J cells were increased after caerulein induced. IRF9 gene silencing upregulated SIRT1, downregulated Ac-p53, and inhibited cell apoptosis, proliferation, and migration. Dual-Luciferase reporter assay showed that IRF9 could negatively regulate SIRT1. The potential mechanism was that IRF9 could modulate cell apoptosis, proliferation, migration, and bind the promoter of SIRT1 to repress SIRT1-p53. It hinted that IRF9 showed a novel function in AP by modulating cell apoptosis, proliferation, migration, and suppressing SIRT1-p53. IRF9 might be a good potential treatment target for AP.

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Acknowledgements

This work was supported by National Natural Science Foundation Incubation Plan (Grant No. 2019GQFY03) and the Doctoral Research Fund Project of the Second Affiliated Hospital of Anhui Medical University (Grant No. 2014BKJ034).

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  1. Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, China

    Bin-Hua Xue, Yi Liu, Hu Chen, Yun Sun & Wei-Li Yu

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B-HX contributed to methodology, software, data curation, and writing-original draft preparation. YL participated in methodology, data curation, and investigation. YS involved in methodology, software, and investigation. HC did investigation. W-LY took part in conceptualization, writing-reviewing and editing, and funding acquisition.

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Correspondence to Wei-Li Yu.

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Xue, BH., Liu, Y., Chen, H. et al. A novel function of IRF9 in acute pancreatitis by modulating cell apoptosis, proliferation, migration, and suppressing SIRT1-p53. Mol Cell Biochem 472, 125–134 (2020). https://doi.org/10.1007/s11010-020-03791-x

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