Functional roles and mechanisms of NAT10-mediated RNA ac4C modification in normal development and cancer progression

TL;DR

This paper reviews how NAT10 enzyme modifies RNA in normal development and cancer, highlighting its role in disease progression and potential as a cancer treatment target.

Contribution

The paper systematically summarizes NAT10's roles in RNA modification and cancer, emphasizing its clinical relevance and therapeutic potential.

Findings

NAT10 is upregulated in multiple cancers and linked to tumor growth and drug resistance.

NAT10 modifies various RNA types, influencing mRNA stability, translation, and non-coding RNA functions.

NAT10 plays roles in embryonic development, stem cell regulation, and immune cell expansion.

Abstract

N-acetyltransferase 10 (NAT10), the primary writer of N4-acetylcytidine (ac4C) on RNA, is broadly upregulated across multiple cancer types and correlates with tumor proliferation, invasion, therapeutic resistance, and poor prognosis, indicating its significant clinical relevance. In this mini review, we systematically summarize the functional roles and mechanisms of NAT10-mediated ac4C modification in both normal development and cancer. Specifically, we cover recent advances in the regulation of mRNA stability and translation, as well as modifications of tRNA, long non-coding RNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA). Moreover, we integrate evidence supporting the essential roles of NAT10 in embryonic development, gametogenesis, stem cell self-renewal and differentiation, cellular architecture and cell cycle control, and immune cell expansion, while outlining its oncogenic contributions to tumor growth, metastasis, metabolic reprogramming, drug resistance, and immune evasion. Based on clinical findings, we discuss the potential of NAT10 as a diagnostic and prognostic biomarker and its application in liquid biopsy, and we evaluate the therapeutic potential and limitations of targeting NAT10, including toxicity, specificity, and resistance. Finally, we propose future research directions, including the tumor-specific mechanisms driving NAT10 upregulation, strategies for selectively targeting cancer versus normal physiology, identification of ac4C readers and erasers, and potential crosstalk between ac4C and chromatin modification, with the aim of advancing NAT10-based precision oncology.

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