Histone lactylation drives oncogenesis by facilitating m⁶A reader protein YTHDF2 expression in ocular melanoma.

IF 12.3 1区生物学 Q1 Agricultural and Biological Sciences Genome Biology Pub Date : 2021-03-16 DOI:10.1186/s13059-021-02308-z

Jie Yu, Peiwei Chai, Minyue Xie, Shengfang Ge, Jing Ruan, Xianqun Fan, Renbing Jia

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引用次数: 1

Abstract

Background: Histone lactylation, a metabolic stress-related histone modification, plays an important role in the regulation of gene expression during M1 macrophage polarization. However, the role of histone lactylation in tumorigenesis remains unclear.

Results: Here, we show histone lactylation is elevated in tumors and is associated with poor prognosis of ocular melanoma. Target correction of aberrant histone lactylation triggers therapeutic efficacy both in vitro and in vivo. Mechanistically, histone lactylation contributes to tumorigenesis by facilitating YTHDF2 expression. Moreover, YTHDF2 recognizes the m6A modified PER1 and TP53 mRNAs and promotes their degradation, which accelerates tumorigenesis of ocular melanoma.

Conclusion: We reveal the oncogenic role of histone lactylation, thereby providing novel therapeutic targets for ocular melanoma therapy. We also bridge histone modifications with RNA modifications, which provides novel understanding of epigenetic regulation in tumorigenesis.

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组蛋白乳酸化通过促进m6A读取器蛋白YTHDF2在眼部黑色素瘤中的表达来驱动肿瘤发生。

背景:组蛋白乳酸化是一种与代谢应激相关的组蛋白修饰，在M1巨噬细胞极化过程中对基因表达的调控中起着重要作用。然而，组蛋白乳酸化在肿瘤发生中的作用尚不清楚。结果:在这里，我们发现组蛋白乳酸化在肿瘤中升高，并与眼部黑色素瘤的不良预后有关。靶校正异常组蛋白乳酸化触发治疗效果在体外和体内。从机制上讲，组蛋白乳酸化通过促进YTHDF2的表达而促进肿瘤发生。此外，YTHDF2识别m6A修饰的PER1和TP53 mrna并促进其降解，从而加速眼部黑色素瘤的发生。结论:我们揭示了组蛋白乳酸化的致瘤作用，从而为眼部黑色素瘤的治疗提供了新的治疗靶点。我们还在组蛋白修饰和RNA修饰之间架起了桥梁，这为肿瘤发生中的表观遗传调控提供了新的理解。

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来源期刊

Genome Biology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-GENETICS & HEREDITY

CiteScore

25.50

自引率

3.30%

发文量

审稿时长

14 weeks

期刊介绍： Genome Biology is a leading research journal that focuses on the study of biology and biomedicine from a genomic and post-genomic standpoint. The journal consistently publishes outstanding research across various areas within these fields. With an impressive impact factor of 12.3 (2022), Genome Biology has earned its place as the 3rd highest-ranked research journal in the Genetics and Heredity category, according to Thomson Reuters. Additionally, it is ranked 2nd among research journals in the Biotechnology and Applied Microbiology category. It is important to note that Genome Biology is the top-ranking open access journal in this category. In summary, Genome Biology sets a high standard for scientific publications in the field, showcasing cutting-edge research and earning recognition among its peers.