Chronic pancreatitis and pancreatic cancer demonstrate active epithelial-mesenchymal transition profile, regulated by miR-217-SIRT1 pathway

被引：93

作者：

Deng, Shichang ^{[1
]}

Zhu, Shuai ^{[1
]}

Wang, Bo ^{[1
]}

Li, Xiang ^{[1
]}

Liu, Yang ^{[1
]}

Qin, Qi ^{[1
]}

Gong, Qiong ^{[1
]}

Niu, Yi ^{[1
]}

Xiang, Cheng ^{[1
]}

Chen, Jingyuan ^{[1
]}

Jin, Yan ^{[1
]}

Deng, Shijiang ^{[1
]}

Yin, Tao ^{[1
]}

Yang, Ming ^{[1
]}

Wu, Heshui ^{[1
]}

Wang, Chunyou ^{[1
]}

Zhao, Gang ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Pancreat Dis Inst, Union Hosp, Tongji Med Coll, Wuhan 430022, Peoples R China

来源：

CANCER LETTERS | 2014年 / 355卷 / 02期

基金：

美国国家科学基金会;

关键词：

miR-217; SIRT1; EMT; Chronic pancreatitis; Pancreatic cancer; TGF-BETA; EXPRESSION; SIRT1; ADENOCARCINOMA; INFLAMMATION; DISEASE; BASICS; CELLS; EMT;

D O I：

10.1016/j.canlet.2014.08.007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Epithelial-mesenchymal transition (EMT) is supposed to be an inflammation induced response which may take a central role in tumorigenesis. Since recent evidence indicates that microRNAs may be involved in EMT, the present study set out to reveal the miRNA which might regulate the EMT in CP (chronic pancreatitis) and PC (pancreatic cancer) and its potential mechanism. Firstly, we provided evidence that both CP and PC tissues demonstrated active EMT profile. Consistently, miR-217 was obviously down-regulated in CP, PC and TGF-beta 1 treated PC cells, while negatively correlated to its direct target SIRT1. Moreover, either ectopic expression of miR-217 or inhibition of SIRT1 remarkably induced mesenchymal to epithelial transition (MET) in TGF-beta 1 treated PC cells. On the contrary, miR-217 inhibitor promoted EMT in PC cells but not in SIRT-knockdown PC cells. Clinical information from a cohort of 54 PC patients demonstrated that down-regulated miR-217 was positively correlated with late tumor stage, lymphatic invasion, vascular infiltration and distant metastasis. These results suggest that the overexpressed TGF-beta 1 in inflammation triggers the deregulation of the miR-217-SIRT1 pathway and then promotes the EMT process, which might be involved in the tumorigenesis of PC. Additionally, miR-217 may function as a novel target and predictor for PC prevention and therapy. (C) 2014 The Authors. Published by Elsevier Ireland Ltd.

引用

页码：184 / 191

页数：8

共 26 条

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