Histone lactylation-driven YTHDC1 promotes hepatocellular carcinoma progression via lipid metabolism remodeling

IF 9.1 1区医学 Q1 ONCOLOGY

Cancer letters Pub Date : 2024-12-24 DOI:10.1016/j.canlet.2024.217426

Wenfei Du , Sheng Tan , Yonglin Peng , Sang Lin , Yunqiang Wu , Keshuo Ding , Changyu Chen , Ruiqi Liu , Yu Cao , Zheyi Li , Sijie Gu , Haoran Feng , Bingbing Wan , Sheng-Ce Tao , Niansong Wang , Ying Fan , Xiaodong Zhao

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引用次数: 0

Abstract

Lipid metabolism reprogramming is critical for the initiation and progression of hepatocellular carcinoma (HCC). However, how the dysregulation of lipid metabolism contributes to HCC development remains largely unknown. Here, we report that the m⁶A reader YTHDC1-mediated epigenetic regulation of the long noncoding RNA NEAT1 activates stearoyl-CoA desaturase (SCD)-associated lipid metabolic processes during HCC progression. Mechanistically, histone lactylation in HCC induces increased expression of YTHDC1, increasing the stability of m⁶A-modified NEAT1. The histone acetyltransferase p300 is then recruited by NEAT1 and activates SCD by increasing the level of histone acetylation at the SCD promoter, thus facilitating HCC progression via hepatocellular lipid metabolism remodeling. Taken together, these discoveries suggest a close link between the epigenetic machinery and lipid metabolic abnormalities, which promotes cancer progression.

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组蛋白乳酸化驱动的YTHDC1通过脂质代谢重塑促进肝细胞癌进展。

脂质代谢重编程对肝细胞癌（HCC）的发生和发展至关重要。然而，脂质代谢失调如何促进HCC的发展仍是未知的。在这里，我们报道m6A读取器ythdc1介导的长链非编码RNA NEAT1的表观遗传调控激活了HCC进展过程中硬脂酰辅酶a去饱和酶（SCD）相关的脂质代谢过程。在机制上，HCC中的组蛋白乳酸化诱导YTHDC1表达增加，增加m6a修饰的NEAT1的稳定性。组蛋白乙酰转移酶p300随后被NEAT1募集，通过增加SCD启动子处的组蛋白乙酰化水平来激活SCD，从而通过肝细胞脂质代谢重塑促进HCC的进展。综上所述，这些发现表明表观遗传机制与促进癌症进展的脂质代谢异常之间存在密切联系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer letters 医学-肿瘤学

CiteScore

17.70

自引率

2.10%

发文量

427

审稿时长

15 days

期刊介绍： Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research. Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy. By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.