Published online Dec 7, 2018. doi: 10.3748/wjg.v24.i45.5120
Peer-review started: September 5, 2018
First decision: October 24, 2018
Revised: November 12, 2018
Accepted: November 13, 2018
Article in press: November 13, 2018
Published online: December 7, 2018
The severity of acute pancreatitis (AP) is inversely related to the rate of apoptosis of pancreatic acinar cells. Our previous study showed that microRNA-22 (miR-22) promotes the apoptosis of pancreatic acinar cells by targeting Erb-b2 receptor tyrosine kinase 3 (ErbB3). However, the underlying mechanism has not been fully elucidated, and the elements that regulate the expression of miR-22 remain unclear.
The downstream signaling pathways that miR-22 regulates pancreatic acinar cell apoptosis have not been fully elucidated. Besides, miR-22 is an exonic microRNA and has its own host gene promoter. In this study, we identified the transcriptional promoter of miR-22 and verified their functions in pancreatic acinar cell apoptosis.
This research aimed to elucidate the underlying mechanism that miR-22 promotes the apoptosis of rat pancreatic acinar cells (AR42J) and identify the transcriptional promoter of miR-22.
MiR-22 promoted the apoptosis of AR42J cells by targeting the ErbB3 gene, and the downstream signaling pathway (PI3k/Akt signaling pathway) was identified using caerulein (Cae)-induced apoptosis of AR42J cells. Furthermore, we predicted the potential transcription promoter of miR-22 and the binding sites using online tools. Luciferase reporter analysis and site-directed mutagenesis indicated the binding site of the glucocorticoid receptor (GR). The binding of GR to the miR-22 promoter in cell culture was identified by a chromatin immunoprecipitation assay.
The results of this study indicated that GR transcriptionally repressed the expression of miR-22 by binding to the miR-22 promoter transcription start site. Downregulation of the expression of GR could upregulate the expression of miR-22. The upregulation of miR-22 promoted the Cae-induced apoptosis of AR42J by targeting ErbB3 and further suppressing the PI3k/Akt signaling pathway.
GR transcriptionally repressed the expression of miR-22 and downregulation of the expression of GR could upregulate the expression of miR-22, which further promoted the Cae-induced apoptosis of AR42J cells.
This study found that GR transcriptionally repressed the expression of miR-22, which might be a target to regulate the expression of miR-22. The further research is to explore the treatment measures for AP by using drugs targeting GR in in vitro cell models and in vivo AP models.