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

Peng，Cheng1,2; Hou，Sheng Tao1; Deng，Chu Xia2; Zhang，Yandong1,3,4

2020

10.1002/jcp.29909

JOURNAL OF CELLULAR PHYSIOLOGY   影响因子和分区

0021-9541

1097-4652

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.

demethylation DHX33 Gadd45a glycolysis RNA helicase Warburg effect

SCI

英语

第一 ; 通讯

Science and Technology Innovation Committee of Shenzhen Municipality[CKCY2017072116462727]

Cell Biology ; Physiology

Cell Biology ; Physiology

WOS:000544902000001

WILEY

MOLECULAR BIOLOGY & GENETICS

2-s2.0-85087297522

Scopus

1.Department of Biology,Southern University of Science and Technology,Shenzhen,China
2.Faculty of Health Sciences,University of Macau,Taipa,Macau,China
3.Shenzhen KeYe Life Technologies,Co.,Ltd.,Shenzhen,China
4.Shenzhen KeYe Life Technologies Co.,Ltd.,Shenzhen,Room 203, Block B, Building 1, Silver Star Intelligence Community II, Guanlan,518110,China

Peng，Cheng,Hou，Sheng Tao,Deng，Chu Xia,et al. Function of DHX33 in promoting Warburg effect via regulation of glycolytic genes[J]. JOURNAL OF CELLULAR PHYSIOLOGY,2020.

Peng，Cheng,Hou，Sheng Tao,Deng，Chu Xia,&Zhang，Yandong.(2020).Function of DHX33 in promoting Warburg effect via regulation of glycolytic genes.JOURNAL OF CELLULAR PHYSIOLOGY.

Peng，Cheng,et al."Function of DHX33 in promoting Warburg effect via regulation of glycolytic genes".JOURNAL OF CELLULAR PHYSIOLOGY (2020).