MiR-652 inhibits acidic microenvironment-induced epithelial-mesenchymal transition of pancreatic cancer cells by targeting ZEB1
Citations Over TimeTop 14% of 2015 papers
Abstract
// Shichang Deng 1, 2, * , Xiang Li 1, * , Yi Niu 1 , Shuai Zhu 1 , Yan Jin 1 , Shijiang Deng 1 , Jingyuan Chen 1 , Yang Liu 1, 2 , Chi He 1 , Tao Yin 1 , Zhiyong Yang 1 , Jing Tao 1 , Jiongxin Xiong 1 , Heshui Wu 1 , Chunyou Wang 1 , Gang Zhao 1 1 Pancreatic Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China 2 Gastrointestinal Surgery, Union Hospital West Campus, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430056, China * These authors have contributed equally to this work Correspondence to: Gang Zhao, e-mail: gangzhao@aliyun.com Chunyou Wang, e-mail: chunyouwang52@126.com Keywords: miR-652, ZEB1, epithelial-mesenchymal transition, acidic microenvironment, pancreatic cancer Received: March 29, 2015 Accepted: October 06, 2015 Published: October 19, 2015 ABSTRACT Recent evidences suggest that the acidic microenvironment might facilitate epithelial mesenchymal transition (EMT) of tumor cells, while the effects of acidity on EMT of pancreatic cancer (PC) remain undefined. The present study demonstrated that acidity suppressed miR-652 expression, which further promoted EMT process by absenting inhibition on the transcriptional factor ZEB1 expression. At first, we found that acidity remarkably enhanced invasion ability of PC cells accompanying with increased mesenchymal and decreased epithelial markers. Meanwhile, miRNAs-microarray showed that miR-652, the potential regulator of ZEB1, was distinctly decreased in acidity-treated PC cells. Furthermore, restoration of miR-652 reversed acidity-induced EMT by inhibiting ZEB1 expression, while miR-652 inhibitor induced EMT in normal PC cells through promoting ZEB1 expression. Nevertheless, knockdown of ZEB1 significantly suppressed acidity-induced EMT in PC cells, but ZEB1 overexpression rescued the EMT which was inhibited by miR-652 overexpression. The in vivo results showed that the tumor growth and liver metastasis were remarkably retarded by both miR-652 overexpression and ZEB1 knockdown. The clinical samples further revealed that miR-652 was decreased in PC tissues and antagonistically correlated with ZEB1 expression, associating with late tumor stage, lymphatic invasion and metastasis. In conclusion, our study indicated a novel acidity/miR-652/ZEB1/EMT axis in the tumorigenesis of PC.
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