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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.

BACKGROUND It is estimated that each year, approximately 30,800 individuals will be diagnosed with leukemia in the United States and 21,700 individuals will die of the disease. Although the overall incidence of leukemia has been declining in the United States, recent reports suggest that incidence rates may be increasing for certain age and racial groups. METHODS Leukemia incidence (including acute lymphoblastic leukemia [ALL], acute myeloid leukemia [AML], chronic myeloid leukemia [CML], and chronic lymphoblastic leukemia [CLL]) and 5‐year survival rates were obtained from the Surveillance, Epidemiology, and End Results (SEER) program. Specific rates for age (birth–19, 20–44, 45–64, and 65 + years), gender, and race (black, white) were also examined. RESULTS A total of 66,404 cases of leukemia were identified for the period 1973–1998 in the nine reporting SEER sites. For children younger than 20 years old, the overall incidence rate of leukemia increased significantly (estimated annual percent change [EAPC] = 0.5%, 95% confidence interval [CI] = 0.1–0.9), whereas the rate decreased significantly among the group 65 years and older (EAPC = − 0.3, 95% CI = − 0.5 to − 0.1). Incidence rates for CLL and CML decreased significantly during this time period, whereas incidence rates for AML remained stable. Children younger than 20 years old experienced a 15% increase in the 5‐year survival rates for both ALL and AML when comparing the two 10‐year periods of 1974–1983 and 1984–1993. In contrast, there was little overall improvement in survival for adults 45 years and older. In particular, there was a notable decrease in the overall 5‐year survival for blacks older than 65 years and for black males older than 44 years. CONCLUSIONS Although the current study confirmed some of the results noted in other populations, the observed overall decline in leukemia survival for blacks is surprising and warrants further investigation. Cancer 2003;97:2229–35. © 2003 American Cancer Society. DOI 10.1002/cncr.11316

Articular cartilage has little regenerative capacity. Recently, genetic lineage tracing experiments have revealed chondrocyte progenitors at the articular surface. We further characterized these progenitors by using genetic approaches. Histone H2B-green fluorescent protein retention revealed that superficial cells divide more slowly than underlying articular chondrocytes. Clonal genetic tracing combined with immunohistochemistry revealed that superficial cells renew their number by symmetric division, express mesenchymal stem cell markers, and generate chondrocytes both asymmetric and symmetric differentiation. Quantitative analysis of cellular kinetics, in combination with phosphotungstic acid-enhanced micro-computed tomography, showed that superficial cells generate chondrocytes and contribute to the growth and reshaping of articular cartilage. Furthermore, we found that cartilage renewal occurs as the progeny of superficial cells fully replace fetal chondrocytes during early postnatal life. Thus, superficial cells are self-renewing progenitors that are capable of maintaining their own population and fulfilling criteria of unipotent adult stem cells. Furthermore, the progeny of these cells reconstitute adult articular cartilage entirely substituting fetal chondrocytes.-Li, L., Newton, P. T., Bouderlique, T., Sejnohova, M., Zikmund, T., Kozhemyakina, E., Xie, M., Krivanek, J., Kaiser, J., Qian, H., Dyachuk, V., Lassar, A. B., Warman, M. L., Barenius, B., Adameyko, I., Chagin, A. S. Superficial cells are self-renewing chondrocyte progenitors, which form the articular cartilage in juvenile mice.