Open AccessDownregulation of ULK 1 by micro RNA ‐372 inhibits the survival of human pancreatic adenocarcinoma cells
Author(s) -
Chen Hongxi,
Zhang Zhipeng,
Lu Yebin,
Song Kun,
Liu Xiwu,
Xia Fada,
Sun Weijia
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13315
Subject(s) - downregulation and upregulation , cell growth , transfection , gene silencing , gene knockdown , chemistry , pancreatic cancer , carcinogenesis , small interfering rna , autophagy , microrna , cell , cell culture , microbiology and biotechnology , cancer research , apoptosis , biology , cancer , gene , biochemistry , genetics
Dysregulation of micro RNA (mi RNA ) expression in various cancers and their role in cancer progression is well documented. The purpose of this study was to investigate the biological role of miR‐372 in human pancreatic adenocarcinoma ( HPAC ). We collected 20 pairs of HPAC tissues and adjacent non‐cancerous tissues to detect miR‐372 expression levels. We transfected BXPC ‐3 and PANC ‐1 cells with miR‐372 inhibitor/mimics to study their effect on cell proliferation, apoptosis, invasion, migration and autophagy. In addition, miR‐372 mimics and a tumor protein UNC 51‐like kinase 1 ( ULK 1) si RNA were co‐transfected into BXPC ‐3 and PANC ‐1 cells to explore the mechanism of miR‐372 and ULK 1 on HPAC tumorigenesis. We found that the expression of miR‐372 was markedly downregulated in HPAC cells compared to adjacent normal tissues. Furthermore, functional assays showed that miR‐372 inhibited cell proliferation, invasion, migration and autophagy in BXPC ‐3 and PANC ‐1 cells. An inverse correlation between miR‐372 expression and ULK 1 expression was observed in HPAC tissues. Downregulation of ULK 1 inhibited the overexpression effects of miR‐372, and upregulation of ULK 1 reversed the effects of overexpressed miR‐372. Finally, we found that silencing ULK 1 or inhibiting autophagy partly rescued the effects of miR‐372 knockdown in HPAC cells, which may explain the influence of miR‐372/ ULK 1 in HPAC development. Taken together, these results revealed a significant role of the miR‐372/ ULK 1 axis in suppressing HPAC cell proliferation, migration, invasion and autophagy.