Abstract
Severe acute pancreatitis (SAP) is the most serious type of pancreatitis with high morbidity and mortality. The underlying mechanism behind SAP pathogenesis is complex and remains elusive. Circular RNAs (circRNAs) are emerging as vital regulators of gene expression in various diseases by sponging microRNAs (miRNAs). However, the roles of circRNAs in the pathophysiology of SAP remain unknown. In the present study, next-generation RNA sequencing was utilized to identify circRNA transcripts in the pancreatic tissues from three SAP mice and three matched normal tissues. The differentially expressed circRNAs were confirmed by real-time PCR, and the biological functions of their interaction with miRNAs and mRNAs were analyzed. Our results demonstrate that 56 circRNAs were differentially expressed in SAP mice compared with normal controls. Six differentially expressed circRNAs were confirmed with the sequencing data. Importantly, we characterized a significantly downregulated circRNA derived from the ZFP664 gene in SAP. CircZFP644 was found to be negatively correlated with miR-21-3p, with a perfectly matched binding sequence to miR-21-3p. In conclusion, CircZFP644 may play an important role in the pathogenesis of SAP through sponging miR-21-3p. Our findings may provide novel insights regarding the workings of the pathophysiological mechanism of SAP and offer novel targets for SAP.
Highlights
Acute pancreatitis (AP) is a common inflammatory disorder of the pancreas with high morbidity and mortality (Peery et al, 2019)
The featured histopathological changes were found in the pancreatic tissues from the Severe acute pancreatitis (SAP) group, including pancreatic lobule interstitial edema, granulocyte infiltration, and extensive acinar cell necrosis (Figure 1A), and the corresponding histopathological scores are presented (Figure 1B)
Numerous studies have explored the molecular mechanisms underlying SAP, and accumulating evidence indicates that non-coding RNAs, especially miRNAs, significantly regulate the function of pancreatic acinar cells to exert an influence on the process of SAP
Summary
Acute pancreatitis (AP) is a common inflammatory disorder of the pancreas with high morbidity and mortality (Peery et al, 2019). 20% of patients with AP develop severe acute pancreatitis (SAP) characterized by extensive pancreatic necrosis and multiple organ failure, resulting in mortality rates as high as 30% (Forsmark et al, 2016). It is critical to address the biological processes and molecular mechanisms underlying the development and progression of SAP so that novel preventive or therapeutic strategies can be created. MiRNAs are the most widely characterized and studied. Functional studies confirm that knockdown of certain miRNAs (e.g., miR-21) can be conducive to the reduction of damage caused by SAP (Ma et al, 2015; Li et al, 2018a). The roles of miRNAs have been well characterized, the precise mechanisms of miRNAs in SAP remain largely unexplored
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