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<p>High-mobility group box 3 (HMGB3) mediates hypoxia-induced glycolysis in various cancers and acts as an oncogene in esophageal carcinoma (EC/ESCA). However, its roles in regulating glycolysis and histone lactylation during EC progression remain unclear. In this study, quantitative polymerase chain reaction (qPCR) and western blotting were conducted to measure HMGB3 levels in EC samples and cells. 5-Ethynyl-2’-deoxyuridine (EdU) assays, colony formation assays, and flow cytometry analyses were conducted to measure cell proliferation and apoptosis. Xenograft mouse models were established to explore tumorigenesis in vivo. Lactate production and glucose uptake were measured using commercial kits. Immunofluorescence staining was used to evaluate the co-localization of c-myc with lysine lactylation (Kla) and Ki67 expression in tumor tissue. A TOP/FOP assay was employed to evaluate Wnt/β-catenin pathway activity. Results revealed upregulated HMGB3 and elevated histone lactylation in EC. HMGB3 knockdown inhibited EC glycolysis, c-myc lactylation, and cell proliferation, yet promoted apoptosis, mimicking the effect of the glycolysis inhibitor 2-deoxy-D-glucose (2-DG). HMGB3 depletion also inactivated the Wnt/β-catenin signaling and impaired xenograft tumor growth, glycolysis, and lactylation. In conclusion, HMGB3 promotes EC malignant progression and tumor growth via histone lactylation and Wnt/β-catenin-mediated c-myc transcriptional activation.</p>

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HMGB3 facilitates malignant phenotype of esophageal carcinoma via histone lactylation- and Wnt/β-catenin-dependent transcription activation of c-myc

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月20日

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  • Ting Qian,
  • Jin Liu,
  • Guochun Cao,
  • Hui Jia,
  • Meng Song,
  • Min Wang,
  • Luni Guo,
  • Qian Zhang,
  • Delin Liu

摘要

High-mobility group box 3 (HMGB3) mediates hypoxia-induced glycolysis in various cancers and acts as an oncogene in esophageal carcinoma (EC/ESCA). However, its roles in regulating glycolysis and histone lactylation during EC progression remain unclear. In this study, quantitative polymerase chain reaction (qPCR) and western blotting were conducted to measure HMGB3 levels in EC samples and cells. 5-Ethynyl-2’-deoxyuridine (EdU) assays, colony formation assays, and flow cytometry analyses were conducted to measure cell proliferation and apoptosis. Xenograft mouse models were established to explore tumorigenesis in vivo. Lactate production and glucose uptake were measured using commercial kits. Immunofluorescence staining was used to evaluate the co-localization of c-myc with lysine lactylation (Kla) and Ki67 expression in tumor tissue. A TOP/FOP assay was employed to evaluate Wnt/β-catenin pathway activity. Results revealed upregulated HMGB3 and elevated histone lactylation in EC. HMGB3 knockdown inhibited EC glycolysis, c-myc lactylation, and cell proliferation, yet promoted apoptosis, mimicking the effect of the glycolysis inhibitor 2-deoxy-D-glucose (2-DG). HMGB3 depletion also inactivated the Wnt/β-catenin signaling and impaired xenograft tumor growth, glycolysis, and lactylation. In conclusion, HMGB3 promotes EC malignant progression and tumor growth via histone lactylation and Wnt/β-catenin-mediated c-myc transcriptional activation.