miR-155-5p is Negatively Associated with Acute Pancreatitis and Inversely Regulates Pancreatic Acinar Cell Progression by Targeting Rela and Traf3

Abstract

Background/Aims: Acute pancreatitis contributes to high mortality in pancreatitis patients, and miRNAs play a vital role in the development of acute pancreatitis (AP), however, its precise biological role remains largely elusive. Methods: To clarify the potential mechanisms of miRNAs in AP, we built mouse models of mild acute pancreatitis (MAP) and moderate/ severe acute pancreatitis (SAP). MiRNA microarray analysis and Real-time quantitative PCR (qRT-PCR) were used to analyze the expression of miRNA in MAP/SAP. TargetScan software, dual-luciferase gene reporter assays and Western blotting were used to assess the target genes of miR-155-5p in AP. Results: miR-155-5p was significantly decreased in MAP/SAP mice compared to controls. In pancreatic acinar AR42J cells transfected with miR-155-5p mimic, the expression of Rela and Traf3 notably decreased in both the caerulein- and TLC-S-induced groups compared with the negative control (NC); however, the expression of Rela and Traf3 notably increased after transfection with miR-155-5p inhibitor. Combined analysis using the TargetScan software and dual-luciferase gene reporter assays indicated that Rela and Traf3 were both targeted by miR-155-5p. Meanwhile, the expression of Ptgs2 also decreased after transfection of the AR42J cells with miR-155-5p mimic. The opposite results were found when miR-155-5p inhibitor was transfected into the AR42J cells. In addition, we treated caerulein- and TLC-S-induced AR42J cells with the Rela inhibitor helenalin and found that the expression of Rela, Traf3 and Ptgs2 decreased compared with the NC, while the expression of miR-155-5p did not show any significant difference. Furthermore, we found that miR-155-5p was significantly down-regulated in pancreatitis patients. Conclusion: miR-155-5p inversely regulated AP development through the Rela/Traf3/Ptgs2 signaling pathway.

Serum microRNAs as novel biomarkers for early prediction of disease severity in patients with acute pancreatitis

“…Lee Hb et al have shown that miR-216a and miR-375 could predict the degree of pancreatic injury in dog model [11].Furthermore, some studies focused on serum miRNAs profiles of SAP patients with a specific organ failure [12,13]. Notably, the miRNAs profile in the present study was quite different from those reported by others [6,[9][10][11][12][13]. One possible reason is that the classifications of enrolled patients were different.…”

“…Several studies have investigated circulating miRNAs in AP patients. An overexpression of miR-155 has been reported to be correlated with SAP [9], but it was also demonstrated to be inversely correlated with SAP in another study [10]. Lee Hb et al have shown that miR-216a and miR-375 could predict the degree of pancreatic injury in dog model [11].Furthermore, some studies focused on serum miRNAs profiles of SAP patients with a specific organ failure [12,13].…”

MicroRNAs in acute pancreatitis: From pathogenesis to novel diagnosis and therapy

“…For example, although most studies reported that miR‐551b‐5p would be elevated in serum in AP, the elevation was not obvious in the study of Lee et al (). In addition, S. Liu et al () found that miR‐155 expression in human serum was lower in patients with AP than in healthy people, and lower in patients with SAP than in patients with mild acute pancreatitis (MAP). On the contrary, Wang found that the expression level of miR‐155 in the serum of patients with SAP was higher than that of MAP (D. Wang et al, ).…”

“…miR‐155 is recognized as the first miRNA to be implicated in immune regulatory functions because it plays critical roles in innate and adaptive immune responses. S. Liu et al () found that the expression of miR‐155 was decreased in serum of patients with AP, and its target genes v‐rel reticuloendotheliosis viral oncogene homolog A ( Rela ) and TNF receptor associated factor 3 ( Traf3 ) were upregulated in pancreatic acinar cells, which in turn enhances the activation of nuclear factor kappa B subunit 1 (NF‐κB) signaling pathway in acinar cells (S. Liu et al, ). The data indicate that downregulation of miR‐155 may exert an influence on pancreatic acinar cells to induce a stronger inflammation.…”

Methionine selenium antagonizes LPS‐induced necroptosis in the chicken liver via the miR‐155/TRAF3/MAPK axis

“…Bioinformatics analysis has found that gga-miR-155 has a potential targeting relationship with TNF receptor-related factor 3 (TRAF3). Liu et al (2018) showed that miR-155-5p reverses the damaged pancreatic acinar cells by targeting TRAF3, thereby alleviating acute pancreatitis. The TRAF family is comprised of intracellular cohesive proteins that bind directly or indirectly to TNF-α and IL-1, which mediates various downstream signaling pathways, thereby affecting cell proliferation, differentiation, and apoptosis, ultimately regulating a variety of biological processes.…”