The tRNA Gm18 methyltransferase TARBP1 promotes hepatocellular carcinoma progression via metabolic reprogramming of glutamine

Shi, Xiaoyan1,2; Zhang, Yangyi1,2; Wang, Yuci1,2; Wang, Jie3; Gao, Yang4,5; Wang, Ruiqi1,2; Wang, Liyong3; Xiong, Minggang1,2,6; Cao, Yanlan1,2; Ou, Ningjing7; Liu, Qi8,9; Ma, Honghui3,10; Cai, Jiabin3; Chen, Hao1,2

2024-06-01

10.1038/s41418-024-01323-4

CELL DEATH AND DIFFERENTIATION   影响因子和分区

1350-9047

1476-5403

Cancer cells rely on metabolic reprogramming to sustain the prodigious energetic requirements for rapid growth and proliferation. Glutamine metabolism is frequently dysregulated in cancers and is being exploited as a potential therapeutic target. Using CRISPR/Cas9 interference (CRISPRi) screening, we identified TARBP1 (TAR (HIV-1) RNA Binding Protein 1) as a critical regulator involved in glutamine reliance of cancer cell. Consistent with this discovery, TARBP1 amplification and overexpression are frequently observed in various cancers. Knockout of TARBP1 significantly suppresses cell proliferation, colony formation and xenograft tumor growth. Mechanistically, TARBP1 selectively methylates and stabilizes a small subset of tRNAs, which promotes efficient protein synthesis of glutamine transporter-ASCT2 (also known as SLC1A5) and glutamine import to fuel the growth of cancer cell. Moreover, we found that the gene expression of TARBP1 and ASCT2 are upregulated in combination in clinical cohorts and their upregulation is associated with unfavorable prognosis of HCC (hepatocellular carcinoma). Taken together, this study reveals the unexpected role of TARBP1 in coordinating the tRNA availability and glutamine uptake during HCC progression and provides a potential target for tumor therapy.

SCI

英语

第一 ; 通讯

Biochemistry & Molecular Biology ; Cell Biology

Biochemistry & Molecular Biology ; Cell Biology

WOS:001244638800001

SPRINGERNATURE

MOLECULAR BIOLOGY & GENETICS

Web of Science

1.Southern Univ Sci & Technol, Joint Lab Guangdong & Hong Kong Univ Vasc Homeosta, Sch Med, Dept Human Cell Biol & Genet, Shenzhen 518055, Peoples R China
2.Southern Univ Sci & Technol, Shenzhen Key Lab Gene Regulat & Syst Biol, Shenzhen 518055, Peoples R China
3.Fudan Univ, Zhongshan Hosp, Dept Liver Surg & Transplantat, Key Lab Carcinogenesis & Canc Invas,Minist Educ,Ke, Shanghai 200032, Peoples R China
4.Sichuan Univ, West China Hosp, Dept Ultrasound, Chengdu 610041, Peoples R China
5.Sichuan Univ, Coll Polymer Sci & Engn, Med X Ctr Mat, State Key Lab Polymer Mat Engn, Chengdu 610065, Peoples R China
6.Univ Hong Kong, Sch Biol Sci, Hong Kong, Peoples R China
7.Nanjing Med Univ, State Key Lab Reprod Med, Nanjing 211166, Peoples R China
8.Guangdong Acad Agr Sci, Rice Res Inst, Guangzhou 510640, Peoples R China
9.Coconstruct Minist & Prov, Key Lab Genet & Breeding High Qual Rice Southern C, Guangzhou 510640, Peoples R China
10.Shenzhen Ruipuxun Acad Stem Cell & Regenerat Med, Shenzhen, Peoples R China

Shi, Xiaoyan,Zhang, Yangyi,Wang, Yuci,et al. The tRNA Gm18 methyltransferase TARBP1 promotes hepatocellular carcinoma progression via metabolic reprogramming of glutamine[J]. CELL DEATH AND DIFFERENTIATION,2024.

Shi, Xiaoyan.,Zhang, Yangyi.,Wang, Yuci.,Wang, Jie.,Gao, Yang.,...&Chen, Hao.(2024).The tRNA Gm18 methyltransferase TARBP1 promotes hepatocellular carcinoma progression via metabolic reprogramming of glutamine.CELL DEATH AND DIFFERENTIATION.

Shi, Xiaoyan,et al."The tRNA Gm18 methyltransferase TARBP1 promotes hepatocellular carcinoma progression via metabolic reprogramming of glutamine".CELL DEATH AND DIFFERENTIATION (2024).