MiR-652 inhibits acidic microenvironment-induced epithelial-mesenchymal transition of pancreatic cancer cells by targeting ZEB1

被引：39

作者：

Deng, Shichang ^{[1
,2
]}

Li, Xiang ^{[1
]}

Niu, Yi ^{[1
]}

Zhu, Shuai ^{[1
]}

Jin, Yan ^{[1
]}

Deng, Shijiang ^{[1
]}

Chen, Jingyuan ^{[1
]}

Liu, Yang ^{[1
,2
]}

He, Chi ^{[1
]}

Yin, Tao ^{[1
]}

Yang, Zhiyong ^{[1
]}

Tao, Jing ^{[1
]}

Xiong, Jiongxin ^{[1
]}

Wu, Heshui ^{[1
]}

Wang, Chunyou ^{[1
]}

Zhao, Gang ^{[1
]}

机构：

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

[2] Huazhong Univ Sci & Technol, Tongji Med Coll, Gastrointestinal Surg, Wuhan 430056, Peoples R China

来源：

ONCOTARGET | 2015年 / 6卷 / 37期

基金：

美国国家科学基金会;

关键词：

miR-652; ZEB1; epithelial-mesenchymal transition; acidic microenvironment; pancreatic cancer; MELANOMA-CELLS; DRUG-RESISTANCE; BLOOD-FLOW; TUMOR; PH; HYPOXIA; EXPRESSION; METASTASIS; MICRORNAS; ACIDOSIS;

D O I：

10.18632/oncotarget.5350

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：39661 / 39675

页数：15

共 37 条

[11] Why do cancers have high aerobic glycolysis? [J].