Yang Yi, Ren Jiandong, Huang Qilin, Wu Jun, Yuan Xiaohui, Jiang Wen, Wen Yi, Tang Lijun, Sun Hongyu
Department of General Surgery & Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command (Chengdu Military General Hospital), Chengdu, China.
College of Medicine, Southwest Jiaotong University, Chengdu, China.
Front Genet. 2020 Mar 12;11:206. doi: 10.3389/fgene.2020.00206. eCollection 2020.
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.
重症急性胰腺炎（SAP）是最严重的胰腺炎类型，具有高发病率和死亡率。SAP发病机制背后的潜在机制复杂且仍不清楚。环状RNA（circRNAs）正作为通过海绵吸附微小RNA（miRNAs）在各种疾病中基因表达的重要调节因子而出现。然而，circRNAs在SAP病理生理学中的作用仍然未知。在本研究中，利用下一代RNA测序来鉴定三只SAP小鼠和三个匹配的正常组织的胰腺组织中的circRNA转录本。通过实时PCR确认差异表达的circRNAs，并分析它们与miRNAs和mRNAs相互作用的生物学功能。我们的结果表明，与正常对照相比，56种circRNAs在SAP小鼠中差异表达。用测序数据确认了六种差异表达的circRNAs。重要的是，我们鉴定出一种在SAP中源自ZFP664基因的显著下调的circRNA。发现CircZFP644与miR-21-3p呈负相关，与miR-21-3p具有完美匹配的结合序列。总之，CircZFP644可能通过海绵吸附miR-21-3p在SAP发病机制中发挥重要作用。我们的发现可能为SAP病理生理机制的运作提供新的见解，并为SAP提供新的靶点。
