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. 2023 Nov 15;37(6):470-478.
doi: 10.7555/JBR.37.20230095.

Histone lactylation promotes cell proliferation, migration and invasion through targeting HMGB1 in endometriosis

Jie Chen  1 , Pengfei Qin  1 , Yanli Sun  1 , Suping Han  2
Affiliations

Histone lactylation promotes cell proliferation, migration and invasion through targeting HMGB1 in endometriosis

Jie Chen et al. J Biomed Res. .

Abstract

Endometriosis is defined as a condition with endometrium-like tissues migrating outside of the pelvic cavity. However, the mechanism of endometriosis is still unclear. Lactate can be covalently modified to lysine residues of histones and other proteins, which is called lactylation. The results showed that the higher level of lactate and lactate dehydrogenase A enhanced the histone H3 lysine 18 lactylation (H3K18lac) in ectopic endometrial tissues and ectopic endometrial stromal cells than that in normal endometrial tissues and normal endometrial stromal cells. Lactate promoted cell proliferation, migration, and invasion in endometriosis. Mechanistically, lactate induced H3K18lac to promote the expression of high-mobility group box 1 (HMGB1) in endometriosis, and HMGB1 knockdown significantly reduced the cell proliferation, migration, and invasion of the lactate-treated cells through the phosphorylation of AKT. In conclusion, lactate could induce histone lactylation to promote endometriosis progression by upregulating the expression of HMGB1, which may provide a novel target for the prevention and treatment of endometriosis.

Keywords: ESCs; HMGB1; endometriosis; lactate; lactylation.

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Conflict of interest statement

The authors reported no conflict of interests.

Figures

Figure 1
Figure 1
The upregulated lactate, LDHA, and H3K18lac levels in ectopic endometrial tissues and eESCs.
Figure 2
Figure 2
Lactate promoted cell proliferation, migration, and invasion of nESCs.
Figure 3
Figure 3
2-DG reduced proliferation, migration, and invasion of eESCs.
Figure 4
Figure 4
Lactate upregulated HMGB1 levels through H3K18lac.
Figure 5
Figure 5
HMGB1 knockdown reversed the role of lactate in endometrial cells.
Figure 6
Figure 6
A schematic representation of how lactate promotes endometriosis progression.
See this image and copyright information in PMC

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