Reciprocal feedback loop of the MALAT1-MicroRNA-194-YAP1 pathway regulates progression of acute pancreatitis

Abstract

Background: Acute pancreatitis (AP) has a high mortality rate and often has serious complications. The Hippo-YAP signaling pathway is mainly involved in cell proliferation and stem cell self-renewal. Recent studies have reported that YAP1 plays a crucial role in pancreatic cancer initiation and acute and chronic pancreatitis (CP). However, the role of YAP1 in AP still needs to be clarified. Material/Methods: To assess the role of YAP1 in the progression of AP, we established a cell model of AP in AR42J cells. AR42J, a rat pancreatic acinar cell line, was stimulated with caerulein to mimic AP-like acinar cell injury. Levels of interleukin (IL)-6 and tumor necrosis factor-a (TNF-a) were measured by ELISA to investigate the role of YAP1 in the progression of AP. Results: The results showed that YAP1 and MALAT1 were the targets of miR-194 and were upregulated in caeruleintreated AR42J cells. Overexpression of MALAT1 or YAP1 can increase the levels of IL-6 and TNF-a secreted by AR42J cells, while miR-194 dramatically counteracts this enhancement effect. Conclusions: Our results demonstrated a regulation loop among MATAL1, miR-194, and YAP1, which dynamically regulates the progression of AP, providing a new therapeutic target for treatment of this disease.