Zhang KD, Hu B, Cen G, Yang YH, Chen WW, Guo ZY, Wang XF, Zhao Q, Qiu ZJ. MiR-301a transcriptionally activated by HIF-2α promotes hypoxia-induced epithelial-mesenchymal transition by targeting TP63 in pancreatic cancer. World J Gastroenterol 2020; 26(19): 2349-2373 [PMID: 32476798 DOI: 10.3748/wjg.v26.i19.2349]
Corresponding Author of This Article
Zheng-Jun Qiu, MD, PhD, Chief Doctor, Professor, Surgeon, Department of General Surgery, Shanghai Key Laboratory of Pancreatic Disease, Shanghai General Hospital, Shanghai Jiaotong University, No. 100, Haining Road, Shanghai 200080, China. qiudoctor@sina.com
Research Domain of This Article
Biochemistry & Molecular Biology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. May 21, 2020; 26(19): 2349-2373 Published online May 21, 2020. doi: 10.3748/wjg.v26.i19.2349
MiR-301a transcriptionally activated by HIF-2α promotes hypoxia-induced epithelial-mesenchymal transition by targeting TP63 in pancreatic cancer
Kun-Dong Zhang, Bin Hu, Gang Cen, Yu-Han Yang, Wei-Wei Chen, Zeng-Ya Guo, Xiao-Feng Wang, Qian Zhao, Zheng-Jun Qiu
Kun-Dong Zhang, Bin Hu, Gang Cen, Yu-Han Yang, Wei-Wei Chen, Zeng-Ya Guo, Xiao-Feng Wang, Zheng-Jun Qiu, Department of General Surgery, Shanghai Key Laboratory of Pancreatic Disease, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai 200080, China
Qian Zhao, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology and Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
Author contributions: Zhang KD prepared the manuscript, which was critically reviewed by all co-authors; Zhao Q and Qiu ZJ designed the study; Zhang KD, Hu B, Cen G, and Yang YH conducted the study; Chen WW, Guo ZY, and Wang XF performed the statistical analyses; Zhang KD, Hu B, and Cen G contributed equally to this work; Zhao Q is an equal corresponding author; all authors approved the final version of the manuscript.
Supported byNational Natural Science Foundation of China, No. 81372640.
Institutional review board statement: This study protocol was reviewed and approved by the Medical Ethics Committee of Shanghai General Hospital.
Institutional animal care and use committee statement: This study protocol was reviewed and approved by the Animal Experimental Ethical Committee of Shanghai General Hospital.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Corresponding author: Zheng-Jun Qiu, MD, PhD, Chief Doctor, Professor, Surgeon, Department of General Surgery, Shanghai Key Laboratory of Pancreatic Disease, Shanghai General Hospital, Shanghai Jiaotong University, No. 100, Haining Road, Shanghai 200080, China. qiudoctor@sina.com
Received: November 18, 2019 Peer-review started: November 18, 2019 First decision: January 19, 2020 Revised: February 20, 2010 Accepted: April 18, 2020 Article in press: April 18, 2020 Published online: May 21, 2020 Processing time: 174 Days and 21.7 Hours
Core Tip
Core tip: In this study, we found that miR-301a expression was increased during the process of hypoxia-induced epithelial-mesenchymal transition (EMT) in pancreatic cancer (PC) cells. miR-301a overexpression facilitated hypoxia-induced EMT, while miR-301a knockout inhibited hypoxia-induced EMT in PC cells. The increased expression of miR-301a was transcriptionally regulated by HIF-2α. In addition, we identified a new target gene of miR-301a, namely, TP63, and confirmed that TP63 was involved in EMT and metastasis of PC cells. Collectively, our data suggest that the newly identified HIF-2α-miR301a-TP63 signaling pathway plays a crucial role in hypoxia-induced EMT in pancreatic ductal adenocarcinoma and that miR-301a may serve as a new prognostic biomarker and candidate miRNA for tumor diagnosis and treatment.
