Abstract
Histone lactylation, a novel epigenetic modification, is regulated by the lactate produced by glycolysis. Glycolysis is activated in various cancers, including gastric cancer (GC). However, the molecular mechanism and clinical impact of histone lactylation in GC remain poorly understood. Here, we demonstrate that histone H3K18 lactylation (H3K18la) is elevated in GC, correlating with a worse prognosis. SIRT1 overexpression decreases H3K18la levels, whereas SIRT1 knockdown increases H3K18la levels in GC cells. RNA-seq analysis demonstrates that lncRNA H19 is markedly downregulated in GC cells with SIRT1 overexpression and those grown under glucose free condition, which confirmed decreased H3K18la levels at its promoter region. H19 knockdown decreased the expression levels of LDHA and H3K18la, and LDHA knockdown impaired H19 and H3K18la expression, suggesting an H19/glycolysis/H3K18la-positive feedback loop. Combined treatment with low doses of the SIRT1-specific activator SRT2104 and the LDHA inhibitor oxamate exerted significant antitumor effects on GC cells, with limited adverse effects on normal gastric cells. The SIRT1-weak/H3K18la-strong signature was found to be an independent prognostic factor in patients with GC. Therefore, SIRT1 acts as a histone delactylase for H3K18, and loss of SIRT1 triggers a positive feedback loop involving H19/glycolysis/H3K18la. Targeting this pathway serves as a novel therapeutic strategy for GC treatment.
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Fig. 1: Aberrant levels of global lactylated-lysine (panKla) and H3K18la predict poorer prognosis in patients with gastric cancer.
Fig. 2: SIRT1 acts as a histone delactylase and suppresses cell proliferation and migration.
Fig. 3: Identification of the downregulated genes via histone delactylation in human gastric cancer cell lines.
Fig. 4: H19 promotes aerobic glycolysis and lactylation, upregulating the expression of glycolysis-related genes, including LDHA.
Fig. 5: Dual treatments, inhibition of glycolysis and activation of SIRT1, exhibits a synergistic effect on cell viability.
Fig. 6: The gastric cancer group with weak SIRT1 and strong H19 experiences worse overall survival and recurrence-free survival than other GC groups.
Data availability
The authors affirm that all data supporting the conclusions of this research are accessible within the article and its Supplementary Information files or can be obtained from the corresponding author upon reasonable request. Our RNA-seq data are registered as GSE276703 and GSE276926.
References
Morgan E, Arnold M, Camargo MC, Gini A, Kunzmann AT, Matsuda T, et al. The current and future incidence and mortality of gastric cancer in 185 countries, 2020–40: a population-based modelling study. Eclinicalmedicine. 2022;47:101404.
ArticlePubMedPubMed CentralGoogle Scholar
Wong MCS, Huang J, Chan PSF, Choi P, Lao XQ, Chan SM, et al. Global incidence and mortality of gastric cancer, 1980–2018. JAMA Netw Open. 2021;4:e2118457.
ArticlePubMedPubMed CentralGoogle Scholar
Totoki Y, Saito-Adachi M, Shiraishi Y, Komura D, Nakamura H, Suzuki A, et al. Multiancestry genomic and transcriptomic analysis of gastric cancer. Nat Genet. 2023;55:581–94.
ArticleCASPubMedGoogle Scholar
Seidlitz T, Schmache T, Garciotaa F, Lee JH, Qin N, Kochall S, et al. Sensitivity towards HDAC inhibition is associated with RTK/MAPK pathway activation in gastric cancer. EMBO Mol Med. 2022;14:e15705.
ArticleCASPubMedPubMed CentralGoogle Scholar
Warburg O. The chemical constitution of respiration ferment. Science. 1928;68:437–43.
ArticleCASPubMedGoogle Scholar
Abbassi-Ghadi N, Kumar S, Huang J, Goldin R, Takats Z, Hanna GB. Metabolomic profiling of oesophago-gastric cancer: a systematic review. Eur J Cancer. 2013;49:3625–37.
ArticleCASPubMedGoogle Scholar
Huang S, Guo Y, Li Z, Zhang Y, Zhou T, You W, et al. A systematic review of metabolomic profiling of gastric cancer and esophageal cancer. Cancer Biol Med. 2020;17:181–98.
ArticleCASPubMedPubMed CentralGoogle Scholar
Chan DA, Sutphin PD, Nguyen P, Turcotte S, Lai EW, Banh A, et al. Targeting GLUT1 and the Warburg effect in renal cell carcinoma by chemical synthetic lethality. Sci Transl Med. 2011;3:94ra70.
ArticleCASPubMedPubMed CentralGoogle Scholar
Wang L, Yang Q, Peng S, Liu X. The combination of the glycolysis inhibitor 2-DG and sorafenib can be effective against sorafenib-tolerant persister cancer cells. Onco Targets Ther. 2019;12:5359–73.
ArticleCASPubMedPubMed CentralGoogle Scholar
Chen J, Xie J, Jiang Z, Wang B, Wang Y, Hu X. Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2. Oncogene. 2011;30:4297–306.
ArticleCASPubMedGoogle Scholar
Feng Y, Xiong Y, Qiao T, Li X, Jia L, Han Y. Lactate dehydrogenase A: a key player in carcinogenesis and potential target in cancer therapy. Cancer Med. 2018;7:6124–36.
ArticlePubMedPubMed CentralGoogle Scholar
Abdel-Wahab AF, Mahmoud W, Al-Harizy RM. Targeting glucose metabolism to suppress cancer progression: prospective of anti-glycolytic cancer therapy. Pharmacol Res. 2019;150:104511.
ArticleCASPubMedGoogle Scholar
Huo M, Zhang J, Huang W, Wang Y. Interplay among metabolism, epigenetic modifications, and gene expression in cancer. Front Cell Dev Biol. 2021;9:793428.
ArticlePubMedPubMed CentralGoogle Scholar
Zhang D, Tang Z, Huang H, Zhou G, Cui C, Weng Y, et al. Metabolic regulation of gene expression by histone lactylation. Nature. 2019;574:575–80.
ArticleCASPubMedPubMed CentralGoogle Scholar
Xie Y, Hu H, Liu M, Zhou T, Cheng X, Huang W, et al. The role and mechanism of histone lactylation in health and diseases. Front Genet. 2022;13:949252.
ArticleCASPubMedPubMed CentralGoogle Scholar
Li W, Zhou C, Yu L, Hou Z, Liu H, Kong L, et al. Tumor-derived lactate promotes resistance to bevacizumab treatment by facilitating autophagy enhancer protein RUBCNL expression through histone H3 lysine 18 lactylation (H3K18la) in colorectal cancer. Autophagy. 2024;20:114–30.
ArticleCASPubMedGoogle Scholar
Yu J, Chai P, Xie M, Ge S, Ruan J, Fan X, et al. Histone lactylation drives oncogenesis by facilitating m(6)A reader protein YTHDF2 expression in ocular melanoma. Genome Biol. 2021;22:85.
ArticleCASPubMedPubMed CentralGoogle Scholar
Yang D, Yin J, Shan L, Yi X, Zhang W, Ding Y. Identification of lysine-lactylated substrates in gastric cancer cells. iScience. 2022;25:104630.
ArticleCASPubMedPubMed CentralGoogle Scholar
Xie B, Lin J, Chen X, Zhou X, Zhang Y, Fan M, et al. CircXRN2 suppresses tumor progression driven by histone lactylation through activating the Hippo pathway in human bladder cancer. Mol Cancer. 2023;22:151.
ArticleCASPubMedPubMed CentralGoogle Scholar
Moreno-Yruela C, Zhang D, Wei W, Baek M, Liu W, Gao J, et al. Class I histone deacetylases (HDAC1-3) are histone lysine delactylases. Sci Adv. 2022;8:eabi6696.
ArticleCASPubMedPubMed CentralGoogle Scholar
Wu QJ, Zhang TN, Chen HH, Yu XF, Lv JL, Liu YY, et al. The sirtuin family in health and disease. Signal Transduct Target Ther. 2022;7:402.
ArticleCASPubMedPubMed CentralGoogle Scholar
Zu H, Li C, Dai C, Pan Y, Ding C, Sun H, et al. SIRT2 functions as a histone delactylase and inhibits the proliferation and migration of neuroblastoma cells. Cell Discov. 2022;8:54.
ArticleCASPubMedPubMed CentralGoogle Scholar
Wang R, Li C, Cheng Z, Li M, Shi J, Zhang Z, et al. H3K9 lactylation in malignant cells facilitates CD8(+) T cell dysfunction and poor immunotherapy response. Cell Rep. 2024;43:114686.
ArticleCASPubMedGoogle Scholar
Wang X, Liu X, Xiao R, Fang Y, Zhou F, Gu M, et al. Histone lactylation dynamics: Unlocking the triad of metabolism, epigenetics, and immune regulation in metastatic cascade of pancreatic cancer. Cancer Lett. 2024;598:217117.
ArticleCASPubMedGoogle Scholar
Blander G, Olejnik J, Krzymanska-Olejnik E, McDonagh T, Haigis M, Yaffe MB, et al. SIRT1 shows no substrate specificity in vitro. J Biol Chem. 2005;280:9780–5.
ArticleCASPubMedGoogle Scholar
Montie HL, Pestell RG, Merry DE. SIRT1 modulates aggregation and toxicity through deacetylation of the androgen receptor in cell models of SBMA. J Neurosci. 2011;31:17425–36.
ArticleCASPubMedPubMed CentralGoogle Scholar
Lee IH, Cao L, Mostoslavsky R, Lombard DB, Liu J, Bruns NE, et al. A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc Natl Acad Sci USA. 2008;105:3374–9.
ArticleCASPubMedPubMed CentralGoogle Scholar
Domanegg K, Sleeman JP, Schmaus A. CEMIP, a promising biomarker that promotes the progression and metastasis of colorectal and other types of cancer. Cancers (Basel). 2022;14:5093.
ArticleCASPubMedGoogle Scholar
Guo W, Zhang C, Feng P, Li M, Wang X, Xia Y, et al. M6A methylation of DEGS2, a key ceramide-synthesizing enzyme, is involved in colorectal cancer progression through ceramide synthesis. Oncogene. 2021;40:5913–24.
ArticleCASPubMedPubMed CentralGoogle Scholar
Hua T, Wang RM, Zhang XC, Zhao BB, Fan SB, Liu DX, et al. ZNF76 predicts prognosis and response to platinum chemotherapy in human ovarian cancer. Biosci Rep. 2021;41:BSR20212026.
ArticleCASPubMedPubMed CentralGoogle Scholar
Mizuguchi Y, Sakamoto T, Hashimoto T, Tsukamoto S, Iwasa S, Saito Y, et al. Identification of a novel PRR15L-RSPO2 fusion transcript in a sigmoid colon cancer derived from superficially serrated adenoma. Virchows Arch. 2019;475:659–63.
ArticleCASPubMedGoogle Scholar
Smits G, Mungall AJ, Griffiths-Jones S, Smith P, Beury D, Matthews L, et al. Conservation of the H19 noncoding RNA and H19-IGF2 imprinting mechanism in therians. Nat Genet. 2008;40:971–6.
ArticleCASPubMedGoogle Scholar
Gan L, Lv L, Liao S. Long non‑coding RNA H19 regulates cell growth and metastasis via the miR‑22‑3p/Snail1 axis in gastric cancer. Int J Oncol. 2019;54:2157–68.
CASPubMedGoogle Scholar
Chen S, Wang H, Xu P, Dang S, Tang Y. H19 encourages aerobic glycolysis and cell growth in gastric cancer cells through the axis of microRNA-19a-3p and phosphoglycerate kinase 1. Sci Rep. 2023;13:17181.
ArticleCASPubMedPubMed CentralGoogle Scholar
Sun L, Li J, Yan W, Yao Z, Wang R, Zhou X, et al. H19 promotes aerobic glycolysis, proliferation, and immune escape of gastric cancer cells through the microRNA-519d-3p/lactate dehydrogenase A axis. Cancer Sci. 2021;112:2245–59.
ArticleCASPubMedPubMed CentralGoogle Scholar
Zhai X, Yang Y, Wan J, Zhu R, Wu Y. Inhibition of LDH-A by oxamate induces G2/M arrest, apoptosis and increases radiosensitivity in nasopharyngeal carcinoma cells. Oncol Rep. 2013;30:2983–91.
ArticleCASPubMedGoogle Scholar
Curry AM, White DS, Donu D, Cen Y. Human sirtuin regulators: the “Success” stories. Front Physiol. 2021;12:752117.
ArticlePubMedPubMed CentralGoogle Scholar
Miyaji N, Nishida K, Tanaka T, Araki D, Kanzaki N, Hoshino Y, et al. Inhibition of knee osteoarthritis progression in mice by administering SRT2014, an activator of silent information regulator 2 ortholog 1. Cartilage. 2021;13:1356S–66S.
ArticleCASPubMedGoogle Scholar
Niu Z, Chen C, Wang S, Lu C, Wu Z, Wang A, et al. HBO1 catalyzes lysine lactylation and mediates histone H3K9la to regulate gene transcription. Nat Commun. 2024;15:3561.
ArticleCASPubMedPubMed CentralGoogle Scholar
Wei S, Zhang J, Zhao R, Shi R, An L, Yu Z, et al. Histone lactylation promotes malignant progression by facilitating USP39 expression to target PI3K/AKT/HIF-1alpha signal pathway in endometrial carcinoma. Cell Death Discov. 2024;10:121.
ArticleCASPubMedPubMed CentralGoogle Scholar
Jang SH, Min KW, Paik SS, Jang KS. Loss of SIRT1 histone deacetylase expression associates with tumour progression in colorectal adenocarcinoma. J Clin Pathol. 2012;65:735–9.
ArticlePubMedGoogle Scholar
Yang Q, Wang B, Gao W, Huang S, Liu Z, Li W, et al. SIRT1 is downregulated in gastric cancer and leads to G1-phase arrest via NF-kappaB/Cyclin D1 signaling. Mol Cancer Res. 2013;11:1497–507.
ArticleCASPubMedGoogle Scholar
Zhang Y, Cai X, Chai N, Gu Y, Zhang S, Ding M, et al. SIRT1 Is Reduced in Gastric Adenocarcinoma and Acts as a Potential Tumor Suppressor in Gastric Cancer. Gastrointestinal Tumors. 2015;2:109–23.
ArticleCASGoogle Scholar
Latifkar A, Ling L, Hingorani A, Johansen E, Clement A, Zhang X, et al. Loss of Sirtuin 1 Alters the Secretome of Breast Cancer Cells by Impairing Lysosomal Integrity. Dev Cell. 2019;49:393–408.e7.
ArticleCASPubMedPubMed CentralGoogle Scholar
Dong G, Wang B, An Y, Li J, Wang X, Jia J, et al. SIRT1 suppresses the migration and invasion of gastric cancer by regulating ARHGAP5 expression. Cell Death Dis. 2018;9:977.
ArticlePubMedPubMed CentralGoogle Scholar
Chu ZY, Yang J, Zheng W, Sun JW, Wang WN, Qian HS. Recent advances on modulation of H2O2 in tumor microenvironment for enhanced cancer therapeutic efficacy. Coordination Chem Rev. 2023;481:215049.
ArticleCASGoogle Scholar
Ohshima K, Nojima S, Tahara S, Kurashige M, Kawasaki K, Hori Y, et al. Serine racemase enhances growth of colorectal cancer by producing pyruvate from serine. Nat Metab. 2020;2:81–96.
ArticleCASPubMedGoogle Scholar
Yegutkin GG, Boison D. ATP and adenosine metabolism in cancer: exploitation for therapeutic gain. Pharmacol Rev. 2022;74:797–822.
ArticlePubMedGoogle Scholar
Hsu WW, Wu B, Liu WR. Sirtuins 1 and 2 are universal histone deacetylases. ACS Chem Biol. 2016;11:792–9.
ArticleCASPubMedGoogle Scholar
Halasa M, Wawruszak A, Przybyszewska A, Jaruga A, Guz M, Kalafut J, et al. H3K18Ac as a marker of cancer progression and potential target of anti-cancer therapy. Cells. 2019;8:485.
ArticleCASPubMedPubMed CentralGoogle Scholar
Barber MF, Michishita-Kioi E, Xi Y, Tasselli L, Kioi M, Moqtaderi Z, et al. SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation. Nature. 2012;487:114–8.
ArticleCASPubMedPubMed CentralGoogle Scholar
Jia J, Zhang X, Zhan D, Li J, Li Z, Li H, et al. LncRNA H19 interacted with miR-130a-3p and miR-17-5p to modify radio-resistance and chemo-sensitivity of cardiac carcinoma cells. Cancer Med. 2019;8:1604–18.
ArticleCASPubMedPubMed CentralGoogle Scholar
Peng F, Wang JH, Fan WJ, Meng YT, Li MM, Li TT, et al. Glycolysis gatekeeper PDK1 reprograms breast cancer stem cells under hypoxia. Oncogene. 2018;37:1062–74.
ArticleCASPubMedGoogle Scholar
Rong Y, Dong F, Zhang G, Tang M, Zhao X, Zhang Y, et al. The crosstalking of lactate-Histone lactylation and tumor. Proteomics Clin Appl. 2023;17:e2200102.
ArticlePubMedGoogle Scholar
Pan RY, He L, Zhang J, Liu X, Liao Y, Gao J, et al. Positive feedback regulation of microglial glucose metabolism by histone H4 lysine 12 lactylation in Alzheimer’s disease. Cell Metab. 2022;34:634–48.e6.
ArticleCASPubMedGoogle Scholar
Liu X, Yang Z, Chen Z, Chen R, Zhao D, Zhou Y, et al. Effects of the suppression of lactate dehydrogenase A on the growth and invasion of human gastric cancer cells. Oncol Rep. 2015;33:157–62.
ArticleCASPubMedGoogle Scholar
Zhao Z, Han F, Yang S, Wu J, Zhan W. Oxamate-mediated inhibition of lactate dehydrogenase induces protective autophagy in gastric cancer cells: involvement of the Akt-mTOR signaling pathway. Cancer Lett. 2015;358:17–26.
ArticleCASPubMedGoogle Scholar
Bertelli AA, Giovannini L, Giannessi D, Migliori M, Bernini W, Fregoni M, et al. Antiplatelet activity of synthetic and natural resveratrol in red wine. Int J Tissue React. 1995;17:1–3.
CASPubMedGoogle Scholar
Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003;425:191–6.
ArticleCASPubMedGoogle Scholar
Yang Q, Wang B, Zang W, Wang X, Liu Z, Li W, et al. Resveratrol inhibits the growth of gastric cancer by inducing G1 phase arrest and senescence in a Sirt1-dependent manner. PLoS One. 2013;8:e70627.
ArticlePubMedPubMed CentralGoogle Scholar
Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, et al. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007;450:712–6.
ArticleCASPubMedPubMed CentralGoogle Scholar
Miller JJ, Fink A, Banagis JA, Nagashima H, Subramanian M, Lee CK, et al. Sirtuin activation targets IDH-mutant tumors. Neuro Oncol. 2021;23:53–62.
ArticleCASPubMedGoogle Scholar
Han L, Long Q, Li S, Xu Q, Zhang B, Dou X, et al. Senescent stromal cells promote cancer resistance through SIRT1 loss-potentiated overproduction of small extracellular vesicles. Cancer Res. 2020;80:3383–98.
ArticleCASPubMedPubMed CentralGoogle Scholar
Krueger JG, Suarez-Farinas M, Cueto I, Khacherian A, Matheson R, Parish LC, et al. A randomized, placebo-controlled study of SRT2104, a SIRT1 activator, in patients with moderate to severe psoriasis. PLoS One. 2015;10:e0142081.
ArticlePubMedPubMed CentralGoogle Scholar
Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. an attempt at a histo-clinical classification. Acta Pathol Microbiol Scand. 1965;64:31–49.
ArticleCASPubMedGoogle Scholar
Sano T, Coit DG, Kim HH, Roviello F, Kassab P, Wittekind C, et al. Proposal of a new stage grouping of gastric cancer for TNM classification: International Gastric Cancer Association staging project. Gastric Cancer. 2017;20:217–25.
ArticlePubMedGoogle Scholar
Japanese Gastric Cancer A. Japanese Gastric Cancer Treatment Guidelines 2021 (6th edition). Gastric Cancer. 2023;26:1–25.
ArticleGoogle Scholar
Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transpl. 2013;48:452–8.
ArticleCASGoogle Scholar
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Acknowledgements
This study received funding support from Grants-in-Aid for Scientific Research (A, JP19H01055; B, JP23H02979, JP23K27670, JP24K02320), and Challenging Research (Exploratory, 20K21627, and 22K19554) by JSPS KAKENHI; and P-CREATE (JP19cm0106540) and Program for Basic and Clinical Research on Hepatitis (JP24fk0210136, JP24fk0210102, JP24fk0210106, JP24fk0210149) by the Japan Agency for Medical Research and Development (AMED); and Research Grant by the Princess Takamatsu Cancer Research Fund. We also thank Editage (https://www.editage.com) for English language editing and BioRender (https://www.biorender.com) for figure creation. Special thanks go to Ms. Hiromi Onari for her clerical assistance.
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Department of Molecular Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Shu Tsukihara, Yoshimitsu Akiyama, Shu Shimada, Megumi Hatano, Yosuke Igarashi, Tomohiko Taniai, Yoshiaki Tanji, Keita Kodera, Koya Yasukawa, Kentaro Umeura, Atsushi Kamachi, Atsushi Nara & Shinji Tanaka
Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
Shu Tsukihara, Yosuke Igarashi, Tomohiko Taniai, Yoshiaki Tanji, Keita Kodera, Toru Ikegami & Ken Eto
Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan
Koya Yasukawa, Kentaro Umeura & Atsushi Kamachi
Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Atsushi Nara & Shinji Tanaka
Department of Gastrointestinal Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Keisuke Okuno, Masanori Tokunaga & Yusuke Kinugasa
Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Hiroto Katoh & Shumpei Ishikawa
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Shu Tsukihara
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Contributions
STsukihara, YA, and STanaka designed the study and wrote the manuscript. STsukihara, YA, and SS performed the cell biology, histopathology, and bioinformatics analyses. STsukihara, YI, TT, YT, KK, KY, KU, AK, AN and KO contributed to data curation. STsukihara, KO, MT, HK, SI contributed to sample collections. YA, SS, MH, MT, TI, KE, and YK helped write, review, and edit the manuscript. STanaka was responsible for the overall content of this study.
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Correspondence to Yoshimitsu Akiyama or Shinji Tanaka.
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This study was approved by the Ethics Committee of the Faculty of Medicine at Tokyo Medical and Dental University (permission no. M2000-1115-04), and written informed consent was obtained from all patients. Patients were anonymously coded in accordance with the ethical guidelines of the Declaration of Helsinki. The mouse procedures were approved by the Institutional Animal Care and Use Committee of Tokyo Medical and Dental University (permission number 0170135 A).
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Tsukihara, S., Akiyama, Y., Shimada, S. et al. Delactylase effects of SIRT1 on a positive feedback loop involving the H19-glycolysis-histone lactylation in gastric cancer. Oncogene (2024). https://doi.org/10.1038/s41388-024-03243-6
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Received:22 July 2024
Revised:21 November 2024
Accepted:28 November 2024
Published:11 December 2024
DOI:https://doi.org/10.1038/s41388-024-03243-6
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