PolG Inhibits Gastric Cancer Glycolysis and Viability by Suppressing PKM2 Phosphorylation
Authors Lv M, Zhang S, Dong Y, Cao L, Guo S
Received 16 November 2020
Accepted for publication 3 February 2021
Published 16 February 2021 Volume 2021:13 Pages 1559—1570
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Prof. Dr. Xueqiong Zhu
Mengzhu Lv,1,* Simeng Zhang,2,* Yuqing Dong,1 Liu Cao,3 Shu Guo1
1Department of Plastic Surgery, China Medical University the First Hospital, Shenyang, 110001, Liaoning Province, People’s Republic of China; 2Department of Medical Oncology, China Medical University the First Hospital, Shenyang, 110001, Liaoning Province, People’s Republic of China; 3Key Laboratory of Medical Cell Biology, Ministry of Education, Institute of Translational Medicine, China Medical University, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, Shenyang, 110001, Liaoning Province, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Shu Guo
Department of Plastic Surgery, China Medical University the First Hospital, No. 155, Nan Jing Street, Heping District, Shenyang, 110001, Liaoning Province, People’s Republic of China
Email [email protected]
Institute of Translational Medicine, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning Province, People’s Republic of China
Tel +86 24 31939630
Fax +86 024 31939630
Email [email protected]
Purpose: Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the third leading cause of cancer-related death. There is a critical need for the development of novel therapies in GC. DNA polymerase gamma (PolG) has been implicated in mitochondrial homeostasis and affects the development of numerous types of cancer, however, its effects on GC and molecular mechanisms remain to be fully determined. The aim of the present research was to clarify the effects of PolG on GC and its possible molecular mechanism of action.
Methods: The GSE62254 dataset was used to predict the effect of PolG on prognostic value in GC patients. Lentivirus-mediated transduction was used to silence PolG expression. Western blot analysis evinced the silencing effect. Co-immunoprecipitation (Co-IP) analysis was performed to explore the potential molecular mechanism of action. Analysis of the glycolysis process in GC cells was also undertaken. Cell proliferation was determined using a CCK-8 (Cell Counting Kit-8) proliferation assay. Cell migration was detected using the Transwell device. Animal experiments were used to measure in vivo xenograft tumor growth.
Results: GC patients with low PolG expression have worse overall survival (OS) and progression-free survival (PFS). PolG binds to PKM2 and affects the activation of Tyr105-site phosphorylation, thus interfering with the glycolysis of GC cells. In vitro tumor formation experiments in mice also confirmed that PolG silencing of GC has a stronger proliferation ability. PolG can suppress GC cell growth both in vivo and in vitro.
Conclusion: Our study reveals a potential molecular mechanism between PolG and the energy metabolic process of GC tumor cells for the first time, suggesting PolG as an independent novel potential therapeutic target for tumor therapy, and providing new ideas for clinical GC treatment.
Keywords: DNA polymerase gamma, energy metabolism, tumor suppressor, PKM protein, stomach neoplasms
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