Melatonin reduces proliferation and promotes apoptosis of bladder cancer cells by suppressing O‐GlcNAcylation of cyclin‐dependent‐like kinase 5

Jinpeng Wu; Zengqi Tan; Hongjiao Li; Meixuan Lin; Yazhuo Jiang; Liang Liang; Qilong Ma; Junjie Gou; Lulu Ning; Xiang Li; Feng Guan

doi:10.1111/jpi.12765

journal article Sep 18, 2021

Melatonin reduces proliferation and promotes apoptosis of bladder cancer cells by suppressing O‐GlcNAcylation of cyclin‐dependent‐like kinase 5

Jinpeng Wu

Zengqi Tan Hongjiao Li

Meixuan Lin Yazhuo Jiang Liang Liang

Qilong Ma Junjie Gou Lulu Ning Xiang Li

Feng Guan

Journal of Pineal Research Vol. 71 No. 3 · Wiley

View at Publisher Save 10.1111/jpi.12765

Abstract

AbstractMelatonin helps to maintain circadian rhythm, exerts anticancer activity, and plays key roles in regulation of glucose homeostasis and energy metabolism. Glycosylation, a form of metabolic flux from glucose or other monosaccharides, is a common post‐translational modification. Dysregulated glycosylation, particularly O‐GlcNAcylation, is often a biomarker of cancer cells. In this study, elevated O‐GlcNAc level in bladder cancer was inhibited by melatonin treatment. Melatonin treatment inhibited proliferation and migration and enhanced apoptosis of bladder cancer cells. Proteomic analysis revealed reduction in cyclin‐dependent‐like kinase 5 (CDK5) expression by melatonin. O‐GlcNAc modification determined the conformation of critical T‐loop domain on CDK5 and further influenced the CDK5 stability. The mechanism whereby melatonin suppressed O‐GlcNAc level was based on decreased glucose uptake and metabolic flux from glucose to UDP‐GlcNAc, and consequent reduction in CDK5 expression. Melatonin treatment, inhibition of O‐GlcNAcylation by OSMI‐1, or mutation of key O‐GlcNAc site strongly suppressed in vivo tumor growth. Our findings indicate that melatonin reduces proliferation and promotes apoptosis of bladder cancer cells by suppressing O‐GlcNAcylation of CDK5.

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Details

Published: Sep 18, 2021
Vol/Issue: 71(3)
License: View

Authors

J

Jinpeng Wu

Key Laboratory of Resource Biology and Biotechnology in Western China Ministry of Education Provincial Key Laboratory of Biotechnology College of Life Sciences Northwest University Xi'an China

Z

Zengqi Tan

Key Laboratory of Resource Biology and Biotechnology in Western China Ministry of Education Provincial Key Laboratory of Biotechnology College of Life Sciences Northwest University Xi'an China

H

Hongjiao Li

Key Laboratory of Resource Biology and Biotechnology in Western China Ministry of Education Provincial Key Laboratory of Biotechnology College of Life Sciences Northwest University Xi'an China

M

Meixuan Lin

Key Laboratory of Resource Biology and Biotechnology in Western China Ministry of Education Provincial Key Laboratory of Biotechnology College of Life Sciences Northwest University Xi'an China

Y

Yazhuo Jiang

Provincial People’s Hospital Xi’an China

L

Liang Liang

Department of Urology The First Affiliated Hospital of Xi'an Jiaotong University Xi'an China

Q

Qilong Ma

Key Laboratory of Resource Biology and Biotechnology in Western China Ministry of Education Provincial Key Laboratory of Biotechnology College of Life Sciences Northwest University Xi'an China

J

Junjie Gou

Key Laboratory of Resource Biology and Biotechnology in Western China Ministry of Education Provincial Key Laboratory of Biotechnology College of Life Sciences Northwest University Xi'an China

L

Lulu Ning

College of Bioresources Chemical and Materials Engineering Shaanxi University of Science & Technology Xi’an China

X

Xiang Li

Institute of Hematology School of Medicine Northwest University Xi’an China

F

Feng Guan

Key Laboratory of Resource Biology and Biotechnology in Western China Ministry of Education Provincial Key Laboratory of Biotechnology College of Life Sciences Northwest University Xi'an China

Funding

National Natural Science Foundation of China Award: 31971211

Natural Science Foundation of Shaanxi Province Award: 2019JZ‐22

Cite This Article

Jinpeng Wu, Zengqi Tan, Hongjiao Li, et al. (2021). Melatonin reduces proliferation and promotes apoptosis of bladder cancer cells by suppressing O‐GlcNAcylation of cyclin‐dependent‐like kinase 5. Journal of Pineal Research, 71(3). https://doi.org/10.1111/jpi.12765

Melatonin reduces proliferation and promotes apoptosis of bladder cancer cells by suppressing O‐GlcNAcylation of cyclin‐dependent‐like kinase 5

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