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

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 hist

SUBMITTER: Yu J 

PROVIDER: S-EPMC7962360 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature