Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
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 by the 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:
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.
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
Research background

Pancreatic cancer is a highly lethal disease that is characterized by metastasis. Uncovering novel functions of metastasis regulators might provide novel predictive and treatment targets.

Research motivation

Aerobic glycolysis has been implicated in multiple processes of cancer progression. However, the impact of the cancer metastasis gene zinc finger E-box-binding homeobox 1 (ZEB1) on aerobic glycolysis has seldom been discussed, and the molecular link is lacking.

Research objectives

To uncover the roles of ZEB1 in aerobic glycolysis regulation and establish the molecular mechanism.

Research methods

ZEB1 was silenced in pancreatic cancer cells to examine its impact on aerobic glycolysis. The impact of ZEB1 on mitochondrion-localized tumor suppressors sirtuin 3 (SIRT3), 4 and 5 was assessed by real-time polymerase chain reaction and western blotting. The transcriptional regulation of ZEB1 on SIRT3 expression was assayed by dual-luciferase and chromatin immunoprecipitation assays. The underlying molecular mechanism that governs the effect of ZEB1 on SIRT3 expression was confirmed by protein interaction, promoter luciferase and chromatin immunoprecipitation assays.

Research results

ZEB1 positively regulated aerobic glycolysis. Mechanistically, ZEB1 regulated aerobic glycolysis by suppression of SIRT3 via interaction with methyl-CpG binding domain protein 1.

Research conclusions

The metastasis gene ZEB1 is an important regulator of aerobic glycolysis.

Research perspectives

The impact of ZEB1 and SIRT3 on the prediction of prognosis and the prospect for targeting metastasis by regulation of glycolysis should be investigated in the future.