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 AND 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-alpha (TNF-alpha) 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 caerulein-treated AR42J cells. Overexpression of MALAT1 or YAP1 can increase the levels of IL-6 and TNF-alpha 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.