Work

DNMT2 inhibits anaplastic thyroid cancer progression by downregulating 5’tiRNAGly-GCC production

Year: 2026

Type: article

Abstract: Complex tRNA methylation modifications collectively maintain the structural integrity and functional efficiency of tRNA. DNA methyltransferase 2 (DNMT2) regulates the m5C methylation status of tRNA, thereby reprogramming its structure and influencing cancer progression. However, the precise mechanisms through which DNMT2 affects tumor development via tRNA methylation remain insufficiently understood. In this study, we demonstrate that reduced DNMT2 expression promotes the progression of anaplastic thyroid carcinoma (ATC). Specifically, in ATC, DNMT2 catalyzes m5C38 methylation on three tRNAs: tRNA-Asp-GUC, tRNA-Gly-GCC, and tRNA-Val-AAC. Loss of DNMT2 leads to an increased abundance of 5’tiRNA Gly-GCC , generated by ANG-mediated cleavage of m5C38-hypomethylated tRNA-Gly-GCC. This 5’tiRNA Gly-GCC directly binds to hnRNPH1, resulting in a reduction of its protein levels. Moreover, combined treatment with a 5’tiRNA Gly-GCC inhibitor and doxorubicin hydrochloride significantly suppresses ATC progression in vivo. Thus, decreased DNMT2 expression facilitates ATC development by promoting the production of 5’tiRNA Gly-GCC . Our findings also highlight the considerable therapeutic potential of targeting 5’tiRNA Gly-GCC in the treatment of ATC.

Source: Cell Death and Disease

DOI: 10.1038/s41419-026-08488-5

Authors: Ruixin Zhou, Baizhao Li, Mingyu Cao, Zhijing Wu, Fada Xia, Xinying Li

Institutions: Central South University, Xiangya Hospital Central South University

Language: English

Topic: RNA modifications and cancer

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,990