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

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资源类型：
Pubmed体系：
作者：
Shi Xiaoyan[1,2] * ; Zhang Yangyi[1,2] * ; Wang Yuci[1,2] * ; Wang Jie[3] * ; Gao Yang[4,5] ; Wang Ruiqi[1,2] ; Wang Liyong[3] ; Xiong Minggang[1,2,6] ; Cao Yanlan[1,2] ; Ou Ningjing[7] ; Liu Qi[8] ; Ma Honghui[3,9] ; Cai Jiabin[4] ; Chen Hao[1,2] ;
机构： [1]Department of Human Cell Biology and Genetics, Joint Laboratory of Guangdong & Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine [2]Shenzhen Key Laboratory of Gene Regulation and Systems Biology, Southern University of Science and Technology, Shenzhen 518055, China. [3]Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Institutes of Biomedical Sciences, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai 200032, China. [4]Department of Ultrasound, West China Hospital, Sichuan University, Chengdu 610041, China. [5]College of Polymer Science and Engineering, Med-X Center for Materials, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China. [6]School of Biological Sciences, The University of Hong Kong, Hong Kong, SAR, China. [7]State Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China. [8]Rice Research Institute, Guangdong Academy of Agricultural Sciences [9]Key Laboratory of Genetics and Breeding of High Quality Rice in Southern China (Coconstruction by Ministry and Province), Guangzhou 510640, China. [10]Shenzhen Ruipuxun Academy for Stem Cell & Regenerative Medicine, Shenzhen, China
出处：
DOI： 10.1038/s41418-024-01323-4
ISSN：

摘要：
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.© 2024. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.

基金：
This work was supported by National Key Research and Development Program of China (2022YFC2702705), National Natural Science Foundation of China (31971330 and 32170586 to HHM, 82272703 to JBC, 32170604 to HC) and the Lingang Laboratory (Grant No.LG-QS-202204-04 to JBC). This work was also supported by Shenzhen Science and Technology Program (20231120115406001 and JCYJ20230807153703008), Pearl River Recruitment Program of Talents (2021QN02Y122) and Department of Health of Guangdong Province (B2021032) to HC, Shenzhen Key Laboratory of Gene Regulation and Systems Biology (Grant No. ZDSYS20200811144002008) from Shenzhen Innovation Committee of Science and Technology and Funding for Scientific Research and Innovation Team of The First Affiliated Hospital of Zhengzhou University (ZYCXTD2023004).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2024]版：
无
最新[2023]版：
大类 | 1 区 生物学
小类 | 1 区 生化与分子生物学 2 区 细胞生物学
第一作者：
第一作者机构： [1]Department of Human Cell Biology and Genetics, Joint Laboratory of Guangdong & Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine [2]Shenzhen Key Laboratory of Gene Regulation and Systems Biology, Southern University of Science and Technology, Shenzhen 518055, China.
共同第一作者：
通讯作者：
通讯机构： [1]Department of Human Cell Biology and Genetics, Joint Laboratory of Guangdong & Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine [2]Shenzhen Key Laboratory of Gene Regulation and Systems Biology, Southern University of Science and Technology, Shenzhen 518055, China. [3]Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Institutes of Biomedical Sciences, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai 200032, China. [9]Key Laboratory of Genetics and Breeding of High Quality Rice in Southern China (Coconstruction by Ministry and Province), Guangzhou 510640, China.
推荐引用方式(GB/T 7714)：
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,doi:10.1038/s41418-024-01323-4.
APA：
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,,
MLA：
Shi Xiaoyan,et al."The tRNA Gm18 methyltransferase TARBP1 promotes hepatocellular carcinoma progression via metabolic reprogramming of glutamine".Cell Death And Differentiation .(2024)

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