Xu WY, Hu QS, Qin Y, Zhang B, Liu WS, Ni QX, Xu J, Yu XJ. Zinc finger E-box-binding homeobox 1 mediates aerobic glycolysis via suppression of sirtuin 3 in pancreatic cancer. World J Gastroenterol 2018; 24(43): 4893-4905 [PMID: 30487699 DOI: 10.3748/wjg.v24.i43.4893]
Corresponding Author of This Article
Xian-Jun Yu, MD, PhD, Professor, Surgeon, Surgical Oncologist, Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Xuhui District, Shanghai 200032, China. yuxianjun@fudanpci.org
Research Domain of This Article
Gastroenterology & Hepatology
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. Nov 21, 2018; 24(43): 4893-4905 Published online Nov 21, 2018. doi: 10.3748/wjg.v24.i43.4893
Zinc finger E-box-binding homeobox 1 mediates aerobic glycolysis via suppression of sirtuin 3 in pancreatic cancer
Wen-Yan Xu, Qiang-Sheng Hu, Yi Qin, Bo Zhang, Wen-Sheng Liu, Quan-Xing Ni, Jin Xu, Xian-Jun Yu
Wen-Yan Xu, Qiang-Sheng Hu, Bo Zhang, Wen-Sheng Liu, Quan-Xing Ni, Xian-Jun Yu, Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
Yi Qin, Jin Xu, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Yi Qin, Bo Zhang, Jin Xu, Pancreatic Cancer Institute, Fudan University, Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
Author contributions: Yu XJ designed and supervised the study; Xu WY performed biochemical assays and wrote the manuscript; Hu QS and Qin Y performed metabolism assays, collected and analyzed the biochemistry and cell biology data; Zhang B and Liu WS helped in The Cancer Genome Atlas (TCGA) dataset analysis and analysis of clinical data; Ni QX and Xu J supervised the organization and editing of the manuscript.
Supported bythe National Science Fund for Distinguished Young Scholars of China, No. 81625016; the National Science Foundation of China, No. 81502031 and No. 81772555; Shanghai Municipal Commission of Health and Family Planning Grant, No. 20154Y0090; and Youth Research Foundation of Shanghai Municipal Commission of Health and Family Planning, No. Z0124Y074.
Conflict-of-interest statement: The authors have declared no conflicts of interest.
Open-Access: 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/
Correspondence to: Xian-Jun Yu, MD, PhD, Professor, Surgeon, Surgical Oncologist, Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Xuhui District, Shanghai 200032, China. yuxianjun@fudanpci.org
Telephone: +86-21-64175590 Fax: +86-21-64031446
Received: July 7, 2018 Peer-review started: July 9, 2018 First decision: August 31, 2018 Revised: September 27, 2018 Accepted: October 15, 2018 Article in press: October 15, 2018 Published online: November 21, 2018 Processing time: 137 Days and 18.2 Hours
Abstract
AIM
To uncover the roles of tumor-promoting gene ZEB1 in aerobic glycolysis regulation and shed light on the underlying molecular mechanism.
METHODS
Endogenous zinc finger E-box binding homeobox-1 (ZEB1) was silenced using a lentivirus-mediated method, and the impact of ZEB1 and methyl-CpG binding domain protein 1 (MBD1) on aerobic glycolysis was measured using seahorse cellular flux analyzers, reactive oxygen species quantification, and mitochondrial membrane potential measurement. The interaction between ZEB1 and MBD1 was assessed by co-immunoprecipitation and immunofluorescence assays. The impact of ZEB1 and MBD1 interaction on sirtuin 3 (SIRT3) expression was confirmed by quantitative polymerase chain reaction, western blotting, and dual-luciferase and chromatin-immunoprecipitation assays.
RESULTS
ZEB1 was a positive regulator of aerobic glycolysis in pancreatic cancer. ZEB1 transcriptionally silenced expression of SIRT3, a mitochondrial-localized tumor suppressor, through interaction with MBD1.
CONCLUSION
ZEB1 silenced SIRT3 expression via interaction with MBD1 to promote aerobic glycolysis in pancreatic cancer.
Core tip: Recent studies have demonstrated the impact of aerobic glycolysis on oncogenesis, proliferation, progression, and metastasis of cancer cells. Zinc finger E-box binding homeobox-1 (ZEB1) is an important regulator of metastasis and progression of pancreatic cancer, but its role in aerobic glycolysis has seldom been discussed. Our results demonstrated that ZEB1 is an important regulator of aerobic glycolysis. It has been demonstrated that ZEB1 regulates aerobic glycolysis by suppression of sirtuin 3 via interaction with methyl-CpG binding domain protein 1. Our results shed light on novel aspects and targets for treatment of pancreatic cancer.
