ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020
Lactate Induces Production of the tRNA
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- tRNA-derived small RNAs in tumor microenvironment remodeling: From mechanistic insights to therapeutic perspectives.Oncogene · 2026Review
- Lactate-induced miR-7-5p/TRIM33 reprograms metabolic flux to suppress tumor growth and viral reactivation.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Pseudouridine synthases upregulate 5'-tRF-Lys to inhibit YPEL3 and drive malignant progression in nasopharyngeal carcinoma.Cellular & molecular biology letters · 2026Article
- Acidic microenvironment-induced LAMC2 expression promotes proliferation, migration, and pathway regulation in non-small cell lung cancer cells.Frontiers in oncology · 2026Article
- Reprogramming the immunosuppressive breast cancer microenvironment: integrating cellular, metabolic, and stromal targets for rational immunotherapy.Frontiers in immunology · 2026Review
- A specific tsRNA in serum from patients with nasopharyngeal carcinoma: 5'tiRNA-32-ValAAC-2 mediates malignance of nasopharyngeal carcinoma cells.Frontiers of medicine · 2025Article
- Review
- The functions and modifications of tRNA-derived small RNAs in cancer biology.Cancer metastasis reviews · 2025Review
- TaqMan RT-qPCR for tRNA half quantification.Methods in enzymology · 2025Article
- cP-RNA-seq for tRNA half sequencing.Methods in enzymology · 2025Article
- Unveiling the hidden world of transfer RNA-derived small RNAs in inflammation.Journal of inflammation (London, England) · 2024Review
- A small molecule that selectively inhibits the growth of Epstein-Barr virus-latently infected cancer cells.iScience · 2024Article
- The tRNAProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Immunostimulatory short non-coding RNAs in the circulation of patients with tuberculosis infection.Molecular therapy. Nucleic acids · 2024Article
- Multiple regulatory roles of the transfer RNA-derived small RNAs in cancers.Genes & diseases · 2024Review
- The impact of glucose metabolism on inflammatory processes in sepsis-induced acute lung injury.Frontiers in immunology · 2024Review
- Lactate's impact on immune cells in sepsis: unraveling the complex interplay.Frontiers in immunology · 2024Review
- Targeting choroidal vasculopathy via up-regulation of tRNA-derived fragment tRF-22 expression for controlling progression of myopia.Journal of translational medicine · 2023Article
- Transfer RNA-derived small RNAs in tumor microenvironment.Molecular cancer · 2023Review
- Soluble markers of B cell activation suggest a role of B cells in the pathogenesis of systemic sclerosis-associated pulmonary arterial hypertension.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High plasma lactate is emerging as a critical regulator in development and progression of many human malignancies. Small RNAs derived from cleavage of mature tRNAs have been implicated in many cellular stresses, but the detailed mechanisms that respond to lactic acid (LA; acidic lactate) are not well defined. Here, using an Epstein-Barr virus (EBV)-immortalized B lymphoblastic cell line (LCL) as a model, we report that LA induces cleavage of mature tRNA at the anticodon loop, particularly production of three 5'-tRNA halves (5'-HisGUG, 5'-ValAAC, and 5'-GlyGCC), along with increased expression of RNA polymerase III and angiogenin (ANG). Of these, only the 5'-HisGUG half binds to the chromatin regulator argonaute-2 (AGO2) instead of the AGO1 protein for stability. Notably, the levels of ANG and 5'-HisGUG half expression in peripheral blood mononuclear cells from B cell lymphoma patients are tightly correlated with lactate dehydrogenase (LDH; a lactate indicator) in plasma. Silencing production of the 5'-HisGUG half by small interfering RNA or inhibition of ANG significantly reduces colony formation and growth of LA-induced tumor cells in vitro and in vivo using a murine xenograft model. Overall, our findings identify a novel molecular therapeutic target for the diagnosis and treatment of B cell lymphoma.
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