BAG3 directly stabilizes Hexokinase 2 mRNA and promotes aerobic glycolysis in pancreatic cancer cells

Author:

An Ming-Xin123,Li Si1,Yao Han-Bing1,Li Chao1,Wang Jia-Mei1,Sun Jia1,Li Xin-Yu1,Meng Xiao-Na1,Wang Hua-Qin123ORCID

Affiliation:

1. Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, China

2. Key Laboratory of Cell Biology, Ministry of Public Health, China Medical University, Shenyang, China

3. Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China

Abstract

Aerobic glycolysis, a phenomenon known historically as the Warburg effect, is one of the hallmarks of cancer cells. In this study, we characterized the role of BAG3 in aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) and its molecular mechanisms. Our data show that aberrant expression of BAG3 significantly contributes to the reprogramming of glucose metabolism in PDAC cells. Mechanistically, BAG3 increased Hexokinase 2 (HK2) expression, the first key enzyme involved in glycolysis, at the posttranscriptional level. BAG3 interacted with HK2 mRNA, and the degree of BAG3 expression altered recruitment of the RNA-binding proteins Roquin and IMP3 to the HK2 mRNA. BAG3 knockdown destabilized HK2 mRNA via promotion of Roquin recruitment, whereas BAG3 overexpression stabilized HK2 mRNA via promotion of IMP3 recruitment. Collectively, our results show that BAG3 promotes reprogramming of glucose metabolism via interaction with HK2 mRNA in PDAC cells, suggesting that BAG3 may be a potential target in the aerobic glycolysis pathway for developing novel anticancer agents.

Funder

National Natural Science Foundation of China

Publisher

Rockefeller University Press

Subject

Cell Biology

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