RT Journal Article
SR Electronic
T1 Novel evidence for an oncogenic role of microRNA-21 in colitis-associated colorectal cancer
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 1470
OP 1481
DO 10.1136/gutjnl-2014-308455
VO 65
IS 9
A1 Chenzhang Shi
A1 Yongzhi Yang
A1 Yang Xia
A1 Yoshinaga Okugawa
A1 Jun Yang
A1 Yong Liang
A1 Hongqi Chen
A1 Peng Zhang
A1 Feng Wang
A1 Huazhong Han
A1 Wen Wu
A1 Renyuan Gao
A1 Christoph Gasche
A1 Huanlong Qin
A1 Yanlei Ma
A1 Ajay Goel
YR 2016
UL http://gut.bmj.com/content/65/9/1470.abstract
AB Objective miR-21 was found to be overexpressed in the colon tissues and serum of patients with UC and colorectal cancer (CRC); however, the exact roles of miR-21 in colitis-associated CRC remain unclear. The aim of our study was to investigate the biological mechanisms of miR-21 in colitis-associated colon cancer (CAC).Design miR-21 expression was examined in the tumours of 62 patients with CRC from China and 37 colitis-associated neoplastic tissues from Japan and Austria. The biological functions of miR-21 were studied using a series of in vitro, in vivo and clinical approaches.Results miR-21 levels were markedly upregulated in the tumours of 62 patients with CRC, 22 patients with CAC, and in a mouse model of CAC. Following azoxymethane and dextran sulfate sodium intervention, miR-21-knockout mice showed reduced expression of proinflammatory and procarcinogenic cytokines (interleukin (IL) 6, IL-23, IL-17A and IL-21) and a decrease in the size and number of tumours compared with the control mouse group. The absence of miR-21 resulted in the reduced expression of Ki67 and the attenuated proliferation of tumour cells with a simultaneous increase in E-cadherin and decrease in β-catenin and SOX9 in the tumours of CAC mice. Furthermore, the absence of miR-21 increased the expression of its target gene PDCD4 and subsequently modulated nuclear factor (NF)-κB activation. Meanwhile, miR-21 loss reduced STAT3 and Bcl-2 activation, causing an increase in the apoptosis of tumour cells in CAC mice.Conclusions These observations provide novel evidence for miR-21 blockade to be a key strategy in reducing CAC.