Effects of Egr1 on pancreatic acinar intracellular trypsinogen activation and the associated ceRNA network.

ABSTRACT: Acute pancreatitis (AP) is a common digestive disorder with high morbidity and mortality. The present study aimed to investigate the expression of early growth response protein 1 (Egr1), and the effect of competing endogenous (ce)RNA network on trypsinogen activation. Pancreatic acinar intracellular trypsinogen activation (PAITA) is an important event in the early stage of AP; however, the underlying mechanisms remain unclear. The present study used taurolithocholic acid 3?sulfate (TLC?S)?treated AR42J cells (pancreatic cell line) to establish a PAITA model. A gene microarray and bioinformatics analysis was performed to identify the potential key targets in PAITA. The results demonstrated that Egr1, an important transcription factor, was significantly overexpressed in PAITA. In Egr1 small interfering (si)RNA?transfected cells, Egr1 expression was decreased and trypsinogen activation was significantly decreased compared with negative control siRNA?transfected cells, indicating that in TLC?S?induced PAITA, overexpression of Egr1 enhanced trypsinogen activation. A ceRNA network [mRNA?microRNA (miRNA/miR)?long non?coding (lnc)RNA] generated using the PAITA model revealed that the effects of Egr1 on PAITA may be regulated by multiple ceRNA pairs, and the lncRNAs (including NONRATT022624 and NONRATT031002) and miRNAs [including Rattus norvegicus (rno)?miR?214?3p and rno?miR?764?5p] included in the ceRNA pairs may serve roles in PAITA by regulating the expression of Egr1. The results of the present study may provide novel targets for researching the underlying mechanisms of, and developing treatments for AP.

SUBMITTER: Gao B 

PROVIDER: S-EPMC7411386 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature