Review Article

Roles and related underlying mechanisms of mitochondrial RNA modification in cancer progression

Ling-zhi Wang1, Tao-yu Yang2, Zi-hui Xiong3, Jian-xin Peng3, Jia-wang Zhou4, Hong-sheng Wang4, Jun-ming He3
1 Department of Anesthesiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China
2 The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
3 Department of Hepatobiliary Surgery, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China
4 Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, State Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
Correspondence to: Jia-wang Zhou: zhoujw77@mail.sysu.edu.cn, Hong-sheng Wang: whongsh@mail.sysu.edu.cn, Jun-ming He: hejunming0101@sina.com,
DOI: 10.1038/s41401-025-01682-9
Received: 22 June 2025
Accepted: 21 September 2025
Advance online: 1 December 2025

Abstract

Mitochondrial RNA modifications refer to modifications that occur across various RNA species within the mitochondria. While the incidence of such modifications is lower than that in the cytoplasm, substantial evidence highlights their pivotal role in facilitating mitochondrial gene expression and precise protein synthesis. Emerging research suggests that these mitochondrial RNA modifications are also significantly involved in the progression of cancer. In this review, we first delve into the diversity of mitochondrial RNA modifications, their potential sites of occurrence, and the enzymes involved in these processes. We evaluate the existing evidence regarding mitochondrial RNA modifications and their significance in cancer progression and investigate the potential of these modifications as promising targets for both preventative strategies and early diagnostic screening. Finally, we deliberate on the trajectory of mitochondrial RNA modifications in the context of cancer progression and how these RNA modifications might pave the way for novel diagnostic and therapeutic approaches for preventive medicine.
Keywords: RNA modifications; mitochondria; methylation; cancer

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