Evodiamine impairs HIF1A histone lactylation to inhibit Sema3A-mediated angiogenesis and PD-L1 by inducing ferroptosis in prostate cancer

Yu, Ying; Huang, Xing; Liang, Chaoqi; Zhang, Peng

doi:10.1016/j.ejphar.2023.176007

Cited by 32 publications

(4 citation statements)

References 67 publications

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“…Changes in H4K5 sites significantly increase the expression of PD-L1, which disables most T cells but also increases the efficacy of immune checkpoint inhibition (ICI) therapy to a certain extent 115 . The same results have been reported in prostate cancer 116 . The inhibitory effect of histone lactylation on T-cell activity has also been found in glioma.…”

Section: Histone Lactylation: Linking Lactate Metabolism To Epigeneti...supporting

confidence: 88%

“…Substantiating their findings, experimental data indicated that p300, a 'Writer' enzyme for lactylation, facilitates histone lactylation to augment YY1 expression, consequently promoting angiogenesis via the downstream fibroblast growth factor (FGF) pathway 118 . Another study on prostate cancer also confirmed the promoting effect of lactylation on tumor angiogenesis 116 . Given the profusion of angiogenic factors and elevated lactate concentrations within the TME, a pertinent inquiry arises: could analogous mechanisms be operative in the TME?…”

Section: Histone Lactylation: Linking Lactate Metabolism To Epigeneti...mentioning

confidence: 75%

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Histone lactylation: from tumor lactate metabolism to epigenetic regulation

Yu,

Yang,

et al. 2024

Int. J. Biol. Sci.

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The Warburg Effect is one of the most well-known cancer hallmarks. This metabolic pattern centered on lactate has extremely complex effects on various aspects of tumor microenvironment, including metabolic remodeling, immune suppression, cancer cell migration, and drug resistance development. Based on accumulating evidence, metabolites are likely to participate in the regulation of biological processes in the microenvironment and to form a feedback loop. Therefore, further revealing the key mechanism of lactate-mediated oncological effects is a reasonable scientific idea. The discovery and refinement of histone lactylation in recent years has laid a firm foundation for the above idea. Histone lactylation is a post-translational modification that occurs at lysine sites on histones. Specific enzymes, known as “writers” and “erasers”, catalyze the addition or removal, respectively, of lactacyl group at target lysine sites. An increasing number of investigations have reported this modification as key to multiple cellular procedures. In this review, we discuss the close connection between histone lactylation and a series of biological processes in the tumor microenvironment, including tumorigenesis, immune infiltration, and energy metabolism. Finally, this review provides insightful perspectives, identifying promising avenues for further exploration and potential clinical application in this field of research.

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Section: Histone Lactylation: Linking Lactate Metabolism To Epigeneti...supporting

confidence: 88%

Section: Histone Lactylation: Linking Lactate Metabolism To Epigeneti...mentioning

confidence: 75%

Histone lactylation: from tumor lactate metabolism to epigenetic regulation

Yu,

Yang,

et al. 2024

Int. J. Biol. Sci.

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“…The study of protein lactylation holds immense promise in elucidating crucial epigenetic mechanisms that underlie yak metabolism. The intricate relationship between lactogenesis and lactate-derived lactylation with various cellular processes, such as oncogenic signaling, , angiogenesis, immune homeostasis, and metabolic reprogramming, underscores its significance. Similarly, in plants, lysine lactylation is prevalent in proteins serving as nutritional reservoirs in rice grains, intricately linked to core carbon metabolism and protein biosynthesis .…”

Section: Discussionmentioning

confidence: 99%

Protein Lactylation Profiles Provide Insights into Molecular Mechanisms Underlying Metabolism in Yak

Wu,

Chai,

Cai

et al. 2024

J. Agric. Food Chem.

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Protein lysine lactylation, a recently discovered post-translational modification (PTM), is prevalent across tissues and cells of diverse species, serving as a regulator of glycolytic flux and biological metabolism. The yak (Bos grunniens), a species that has inhabited the Qinghai−Tibetan Plateau for millennia, has evolved intricate adaptive mechanisms to cope with the region's unique geographical and climatic conditions, exhibiting remarkable energy utilization and metabolic efficiency. Nonetheless, the specific landscape of lysine lactylation in yaks remains poorly understood. Herein, we present the first comprehensive lactylome profile of the yak, effectively identifying 421, 308, and 650 lactylated proteins in the heart, muscles, and liver, respectively. These lactylated proteins are involved in glycolysis/gluconeogenesis, the tricarboxylic acid cycle, oxidative phosphorylation, and metabolic process encompassing carbohydrates, lipids, and proteins during both anaerobic and aerobic glucose bio-oxidation, implying their crucial role in material and energy metabolism, as well as in maintaining homeostasis in yaks.

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“…In prostate cancer, histone lactylation affects cancer cell plasticity and leads to transcriptional surges of neuroendocrine genes ( He et al, 2023 ). It has been reported that evodiamine blocked histone lactylation in PCa cells, further enhancing Sema3A transcription while inhibiting that of PD-L1 ( Yu et al, 2023 ). Besides, HIF1α lactylation enhances KIAA1199 transcription to promote angiogenesis and vasculogenic mimicry in PCa ( Luo et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Constructing lactylation-related genes prognostic model to effectively predict the disease-free survival and treatment responsiveness in prostate cancer based on machine learning

Pan,

Zhang,

Lin

et al. 2024

Front. Genet.

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Background: Prostate cancer (PCa) is one of the most common malignancies in men with a poor prognosis. It is therefore of great clinical importance to find reliable prognostic indicators for PCa. Many studies have revealed the pivotal role of protein lactylation in tumor development and progression. This research aims to analyze the effect of lactylation-related genes on PCa prognosis.Methods: By downloading mRNA-Seq data of TCGA PCa, we obtained the differential genes related to lactylation in PCa. Five machine learning algorithms were used to screen for lactylation-related key genes for PCa, then the five overlapping key genes were used to construct a survival prognostic model by lasso cox regression analysis. Furthermore, the relationships between the model and related pathways, tumor mutation and immune cell subpopulations, and drug sensitivity were explored. Moreover, two risk groups were established according to the risk score calculated by the five lactylation-related genes (LRGs). Subsequently, a nomogram scoring system was established to predict disease-free survival (DFS) of patients by combining clinicopathological features and lactylation-related risk scores. In addition, the mRNA expression levels of five genes were verified in PCa cell lines by qPCR.Results: We identified 5 key LRGs (ALDOA, DDX39A, H2AX, KIF2C, RACGAP1) and constructed the LRGs prognostic model. The AUC values for 1 -, 3 -, and 5-year DFS in the TCGA dataset were 0.762, 0.745, and 0.709, respectively. The risk score was found a better predictor of DFS than traditional clinicopathological features in PCa. A nomogram that combined the risk score with clinical variables accurately predicted the outcome of the patients. The PCa patients in the high-risk group have a higher proportion of regulatory T cells and M2 macrophage, a higher tumor mutation burden, and a worse prognosis than those in the low-risk group. The high-risk group had a lower IC50 for certain chemotherapeutic drugs, such as Docetaxel, and Paclitaxel than the low-risk group. Furthermore, five key LRGs were found to be highly expressed in castration-resistant PCa cells.Conclusion: The lactylation-related genes prognostic model can effectively predict the DFS and therapeutic responses in patients with PCa.

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Evodiamine impairs HIF1A histone lactylation to inhibit Sema3A-mediated angiogenesis and PD-L1 by inducing ferroptosis in prostate cancer

Cited by 32 publications

References 67 publications

Histone lactylation: from tumor lactate metabolism to epigenetic regulation

Histone lactylation: from tumor lactate metabolism to epigenetic regulation

Protein Lactylation Profiles Provide Insights into Molecular Mechanisms Underlying Metabolism in Yak

Constructing lactylation-related genes prognostic model to effectively predict the disease-free survival and treatment responsiveness in prostate cancer based on machine learning

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