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13 September 2019 : Laboratory Research  

Reciprocal Feedback Loop of the MALAT1-MicroRNA-194-YAP1 Pathway Regulates Progression of Acute Pancreatitis

Lina Gu1BCF, Jingyao Liu2CDF, Dan Xu3BC, Ying Lu1ADEG*

DOI: 10.12659/MSM.915598

Med Sci Monit 2019; 25:6894-6904

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-α (TNF-α) 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-α 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.

Keywords: RNA, Long Noncoding, MicroRNAs, Apoptosis Regulatory Proteins, Base Sequence, Cell Line, Ceruletide, Cytoprotection, Disease Progression, Down-Regulation, Feedback, Physiological, Protein Binding, Signal Transduction, Up-Regulation, YAP-Signaling Proteins

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750