Published online Nov 21, 2018. doi: 10.3748/wjg.v24.i43.4893
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
To uncover the roles of tumor-promoting gene ZEB1 in aerobic glycolysis regulation and shed light on the underlying molecular mechanism.
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.
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.
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.