缺氧促进食管鳞状细胞癌（ESCC）的肿瘤发生和乳酸积累。乳酸可以诱导组蛋白赖氨酸乳酰化（Kla，最近发现的一种组蛋白标记）来调节转录。然而，组蛋白 Kla 在 ESCC 缺氧条件下的功能后果仍有待探索。在这里，我们发现缺氧促进组蛋白 H3K9la 增强 LAMC2 转录，从而促进 ESCC 的增殖。我们发现缺氧下 Kla 的整体水平升高，因此通过定量蛋白质组学鉴定了 ESCC 中组蛋白 Kla 的分布。此外，我们发现缺氧诱导 H3K9la 水平显着增加。接下来，MNase ChIP-seq 和 RNA-seq 分析表明 H3K9la 在细胞连接基因的启动子处富集。最后，我们通过体内和体外实验证明组蛋白 H3K9la 促进 LAMC2 的表达以促进 ESCC 侵袭。简而言之，我们的研究揭示了缺氧引发的组蛋白 Kla 在癌症中的重要作用。© 2024 作者。

Hypoxia promotes tumorigenesis and lactate accumulation in esophageal squamous cell carcinoma (ESCC). Lactate can induce histone lysine lactylation (Kla, a recently identified histone marks) to regulate transcription. However, the functional consequence of histone Kla under hypoxia in ESCC remains to be explored. Here, we reveal that hypoxia facilitates histone H3K9la to enhance LAMC2 transcription for proliferation of ESCC. We found that global level of Kla was elevated under hypoxia, and thus identified the landscape of histone Kla in ESCC by quantitative proteomics. Furthermore, we show a significant increase of H3K9la level induced by hypoxia. Next, MNase ChIP-seq and RNA-seq analysis suggest that H3K9la is enriched at the promoter of cell junction genes. Finally, we demonstrate that the histone H3K9la facilitates the expression of LAMC2 for ESCC invasion by in vivo and in vitro experiments. Briefly, our study reveals a vital role of histone Kla triggered by hypoxia in cancer.© 2024 The Author(s).