Abstract
BackgroundAcute pancreatitis (AP) is a common inflammatory disorder. MicroRNAs play crucial roles in the pathogenesis of AP. In this article, we explored the detailed role and molecular mechanisms of miR-146b-3p in AP progression.MethodsThe rat AR42J cells were treated with cerulein to establish the AP model in vitro. The miR-146b-3p and Annexin A2 (Anxa2) mRNA levels were assessed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Cell viability and apoptosis were tested using the Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. Caspase-3 activity and the production of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay and qRT-PCR. Targeted interaction between miR-146b-3p and Anxa2 was verified by the dual-luciferase reporter and RNA immunoprecipitation assays. Western blot analysis was performed to detect the expression of Anxa2 protein.ResultsOur data revealed that miR-146b-3p was significantly downregulated in AP samples. The enforced expression of miR-146b-3p alleviated cerulein-induced injury in AR42J cells, as evidenced by the promotion in cell viability and the repression in cell apoptosis, as well as the reduction in IL-1β, IL-6, and TNF-α production. Anxa2 was directly targeted and inhibited by miR-146b-3p. Moreover, the alleviative effect of miR-146b-3p overexpression on cerulein-induced AR42J cell injury was mediated by Anxa2.ConclusionsThe current work had led to the identification of miR-146b-3p overexpression that protected against cerulein-induced injury in AR42J cells at least in part by targeting Anxa2, revealing a promising target for AP diagnosis and treatment.
Highlights
Acute pancreatitis (AP) is the most common gastrointestinal disease worldwide [1,2]
3.1 MiR-146b-3p expression is downregulated and Annexin A2 (Anxa2) level is upregulated in AP samples
Anxa2 mRNA was remarkably overexpressed in the serum samples of AP patients compared with the normal control (Figure 1c)
Summary
Acute pancreatitis (AP) is the most common gastrointestinal disease worldwide [1,2]. Despite advances in diagnostic and therapeutic techniques, AP is still associated with significant mortality [4]. A more precise understanding of the molecular basis of AP pathogenesis is crucial for developing better therapeutic interventions. MicroRNAs (miRNAs) are small non-coding RNAs, approximately 19–23 nucleotides long, which play important roles in almost all biological pathways [5]. Emerging evidence has shown the crucial involvement of miRNAs in various diseases, including AP [7,8]. Miao et al uncovered that miR-148a weakened cerulein-induced autophagy in the AP cell model by targeting interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway [9]. Wang et al reported that the reduced level of miR-155 diminished AP’s progression by regulating the Th17/Treg ratio via targeting suppressor of cytokine signaling 3 [10]
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