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

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 m<sup>6</sup>A 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 m<sup>6</sup>A-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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Publication Details

Journal
Cancer Letters
Published
2024-12-24
DOI
https://doi.org/10.1016/j.canlet.2024.217426
Citations
22
Primary Topic
RNA modifications and cancer
Type
article
Field-Weighted Citation Impact
5.14
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article

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

Sijie Gu, Sheng Tan, Yunqiang Wu, Yonglin Peng et al.
22 citations
Cancer Letters
RNA modifications and cancer
5.14
article

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

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

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 m<sup>6</sup>A 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 m<sup>6</sup>A-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.

Cancer LettersVol. 611
Shanghai Jiao Tong University (CN), Anhui Medical University (CN), First Affiliated Hospital of Anhui Medical University (CN), Shanghai Sixth People's Hospital (CN)
Openalex Percentile: Top 4%
RNA modifications and cancer
5.14
DOIOpen Access PDFOpenAlex
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