Oncotarget

Research Papers: Autophagy and Cell Death:

miR-352 participates in the regulation of trypsinogen activation in pancreatic acinar cells by influencing the function of autophagic lysosomes

Zonggong Song _, Yongming Huang, Chao Liu, Ming Lu, Zhituo Li, Bei Sun, Weihui Zhang and Dongbo Xue

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Oncotarget. 2018; 9:10868-10879. https://doi.org/10.18632/oncotarget.24220

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Abstract

Zonggong Song1, Yongming Huang1, Chao Liu 1, Ming Lu2, Zhituo Li1, Bei Sun1, Weihui Zhang1 and Dongbo Xue1

1Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China

2Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

Correspondence to:

Dongbo Xue, email: dongbo_xue@126.com

Keywords: acute pancreatitis; miR-352; LAMP2; CTSL1; autophagic lysosomes

Received: March 03, 2017     Accepted: December 05, 2017     Published: January 13, 2018

ABSTRACT

This study was performed to screen miRNAs and mRNAs that are differentially expressed during trypsinogen activation in acute pancreatitis and to verify their role in the process of trypsinogen activation. The function enrichment analysis showed that the functions of miR-352 and its regulatory targets lysosome-associated membrane protein 2 (LAMP2) and cathepsin L1 (CTSL1) were lysosome related. The results of the verification experiment showed that in the TLC-S-treated AR42J (pancreatic cell line) cells, miR-352 expression increased, expression levels of LAMP2 and CTSL1 were significantly reduced, trypsinogen activation was increased, and the autophagy pathway was blocked. In the miR-352 mimic-transfected cells, miR-352 expression increased, expression levels of LAMP2 and CTSL1 were significantly reduced, trypsinogen activation was increased, intracellular lysosomal pH increased, cathepsins L activity decreased and the amount of autophagolysosomes increased. In the miR-352 inhibitor-transfected cells, miR-352 expression was reduced, expression levels of LAMP2 and CTSL1 were significantly increased, trypsinogen activation was decreased, intracellular lysosomal pH decreased, cathepsins L activity increased and the amount of autophagolysosomes decreased. In the process of taurolithocholic acid 3-sulfate (TLC-S) induced trypsinogen activation, overexpression of miR-352 could down-regulate LAMP2 and CTSL1, resulting in the dysfunction of autophagic lysosome. Thus, the autophagy pathway was blocked, and trypsinogen activation was enhanced.


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