1. Academic Validation
  2. Function of DHX33 in promoting Warburg effect via regulation of glycolytic genes

Function of DHX33 in promoting Warburg effect via regulation of glycolytic genes

  • J Cell Physiol. 2021 Feb;236(2):981-996. doi: 10.1002/jcp.29909.
Cheng Peng 1 2 Sheng-Tao Hou 1 Chu-Xia Deng 2 Yandong Zhang 1 3
Affiliations

Affiliations

  • 1 Department of Biology, Southern University of Science and Technology, Shenzhen, Guangdong, China.
  • 2 Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
  • 3 Shenzhen KeYe Life Technologies, Co., Ltd., Shenzhen, Guangdong, China.
Abstract

Cancer cells metabolize glucose through glycolysis to promote cell proliferation even with abundant oxygen. Multiple glycolysis genes are deregulated during Cancer development. Despite intensive effort, the cause of their deregulation remains incompletely understood. Here in this study, we discovered that DHX33 plays a critical role in Warburg effect of Cancer cells. DHX33 deficient cells have markedly reduced glycolysis activity. Through RNA-seq analysis, we found multiple critical genes involved in Warburg effect were downregulated after DHX33 deficiency. These genes include Lactate Dehydrogenase A (LDHA), pyruvate dehydrogenase kinase 1 (PDK1), Pyruvate Kinase muscle isoform 2 (PKM2), Enolase 1 (ENO1), ENO2, Hexokinase 1/2, among Others. With LDHA, PDK1, and PKM2 as examples, we further revealed that DHX33 altered the epigenetic marks around the promoter of glycolytic genes. This is through DHX33 in complex with Gadd45a-a growth arrest and DNA damage protein. DHX33 is required for the loading of Gadd45a and DNA dioxygenase TET1 at the promoter sites, which resulted in active DNA demethylation and enhanced histone H4 acetylation. We conclude that DHX33 changes local epigenetic marks in favor of the transcription of glycolysis genes to promote Cancer cell proliferation. Our study highlights the significance of RNA helicase DHX33 in Warburg effect and Cancer therapeutics.

Keywords

DHX33; Gadd45a; RNA helicase; Warburg effect; demethylation; glycolysis.

Figures
Products