Molecule Information

General Information of the Molecule (ID: Mol04035)

• Name: Histone H3 ,Homo sapiens
• Synonyms: Histone H3/a; Histone H3/b; Histone H3/c; Histone H3/d; Histone H3/f; Histone H3/h; Histone H3/i; Histone H3/j; Histone H3/k; Histone H3/l
• Molecule Type: Protein
• Gene Name: H3C1
• Gene ID: 8350; 8351; 8352; 8353; 8354; 8355; 8356; 8357; 8358; 8968
• Location: chr6:26195164-26197286[-]
• Sequence:
  MARTKQTARKSTGGKAPRKQLATKAARKSAPATGGVKKPHRYRPGTVALREIRRYQKSTE
  LLIRKLPFQRLVREIAQDFKTDLRFQSSAVMALQEACEAYLVGLFEDTNLCAIHAKRVTI
  MPKDIQLARRIRGERA
• 3D-structure: PDB ID: 7MJU; Classification: Peptide binding protein; Method: X-ray diffraction; Resolution: 2.10 Å
• Function: Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
• Uniprot ID: H31_HUMAN
• Ensembl ID: ENSG00000197409
• HGNC ID: HGNC:4766; HGNC:4775; HGNC:4771; HGNC:4774; HGNC:4776; HGNC:4768; HGNC:4767; HGNC:4769; HGNC:4773; HGNC:4772

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 9 drug(s) in total

Bevacizumab

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Colorectal cancer [ICD-11: 2B91.1] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Colorectal cancer [ICD-11: 2B91.1]
• Resistant Drug: Bevacizumab
• Molecule Alteration: Lactylation; H3K18la
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT-116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: SW620 cells; Colon; Homo sapiens (Human); CVCL_0547
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: 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.

Disease Class: Colorectal cancer [ICD-11: 2B91.1] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Colorectal cancer [ICD-11: 2B91.1]
• Resistant Drug: Bevacizumab
• Molecule Alteration: Lactylation; H3K18la
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Patient-derived xenograft (PDX) mice; Mice
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Quantification viability of patient-derived organoids
• Mechanism Description: 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.

Disease Class: Colorectal cancer [ICD-11: 2B91.1] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Colorectal cancer [ICD-11: 2B91.1]
• Resistant Drug: Bevacizumab
• Molecule Alteration: Lactylation; H3K18la
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Patient-derived xenograft (PDX) mice; Mice
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Tumor weight assay
• Mechanism Description: 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.

Disease Class: Colorectal cancer [ICD-11: 2B91.1] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Colorectal cancer [ICD-11: 2B91.1]
• Resistant Drug: Bevacizumab
• Molecule Alteration: Lactylation; H3K18la
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT-116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: SW620 cells; Colon; Homo sapiens (Human); CVCL_0547
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Western blot assay
• Mechanism Description: 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.

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Bladder cancer [ICD-11: 2C94.0] [2]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Bladder cancer [ICD-11: 2C94.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Lactylation; H3K19la
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: BCa cells; Bladder; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: Notably, we observed that H3 lysine 18 lactylation (H3K18la) plays a crucial role in activating the transcription of target genes by enriching in their promoter regions. Targeted inhibition of H3K18la effectively restored cisplatin sensitivity in these cisplatin-resistant epithelial cells. Furthermore, H3K18la-driven key transcription factors YBX1 and YY1 promote cisplatin resistance in BCa.

Docetaxel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Oral squamous cell carcinoma [ICD-11: 2B6E.0] [3]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Docetaxel
• Molecule Alteration: Lactylation; .
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: OSCC samples; Homo Sapiens
• Mechanism Description: We found that histone Kla-induced BCAM was overexpressed in OSCC, and a high BCAM level was related to a lower immune cell score and inhibition of immune response. On the other hand, BCAM induced EMT and angiogenesis, leading to OSCC malignant progression via activating the Notch signaling pathway. However, the difference of the BCAM function in Pan-cancers might be attributed to tumor heterogeneity. Taken together, BCAM played a vital role in OSCC chemotherapy resistance and prognosis and contributed to inhibition of the immune process, suggesting that it might be a novel therapeutic target for OSCC.

IgG isotype

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.02] [4]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Resistant Drug: IgG isotype
• Molecule Alteration: Lactylation; H3K18la
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Immunocompetent mice inoculated with control Hepa1-6 cells; Mice
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: SRSF10 was upregulated in various tumors and associated with poor prognosis. Moreover, SRSF10 positively regulated lactate production, and SRSF10/glycolysis/ histone H3 lysine 18 lactylation (H3K18la) formed a positive feedback loop in tumor cells. Increased lactate levels promoted M2 macrophage polarization, thereby inhibiting CD8 T cell activity.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.02] [4]

• Metabolic Type: Glucose metabolism
• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Sensitive Drug: IgG isotype
• Molecule Alteration: Lactylation; H3K18la
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Immunocompetent mice inoculated with shSrsf10 cells; Mice
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: SRSF10 was upregulated in various tumors and associated with poor prognosis. Moreover, SRSF10 positively regulated lactate production, and SRSF10/glycolysis/ histone H3 lysine 18 lactylation (H3K18la) formed a positive feedback loop in tumor cells. Increased lactate levels promoted M2 macrophage polarization, thereby inhibiting CD8 T cell activity.

Oxaliplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Oral squamous cell carcinoma [ICD-11: 2B6E.0] [3]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Oxaliplatin
• Molecule Alteration: Lactylation; .
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: OSCC samples; Homo Sapiens
• Mechanism Description: We found that histone Kla-induced BCAM was overexpressed in OSCC, and a high BCAM level was related to a lower immune cell score and inhibition of immune response. On the other hand, BCAM induced EMT and angiogenesis, leading to OSCC malignant progression via activating the Notch signaling pathway. However, the difference of the BCAM function in Pan-cancers might be attributed to tumor heterogeneity. Taken together, BCAM played a vital role in OSCC chemotherapy resistance and prognosis and contributed to inhibition of the immune process, suggesting that it might be a novel therapeutic target for OSCC.

Palbociclib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Oral squamous cell carcinoma [ICD-11: 2B6E.0] [3]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Palbociclib
• Molecule Alteration: Lactylation; .
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: OSCC samples; Homo Sapiens
• Mechanism Description: We found that histone Kla-induced BCAM was overexpressed in OSCC, and a high BCAM level was related to a lower immune cell score and inhibition of immune response. On the other hand, BCAM induced EMT and angiogenesis, leading to OSCC malignant progression via activating the Notch signaling pathway. However, the difference of the BCAM function in Pan-cancers might be attributed to tumor heterogeneity. Taken together, BCAM played a vital role in OSCC chemotherapy resistance and prognosis and contributed to inhibition of the immune process, suggesting that it might be a novel therapeutic target for OSCC.

PD-1 mAb

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.02] [4]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Resistant Drug: PD-1 mAb
• Molecule Alteration: Lactylation; H3K18la
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Control into wild-type C57B/6 mice; Mice
• Experiment for Molecule Alteration: Western blot analysis
• Mechanism Description: SRSF10 was upregulated in various tumors and associated with poor prognosis. Moreover, SRSF10 positively regulated lactate production, and SRSF10/glycolysis/ histone H3 lysine 18 lactylation (H3K18la) formed a positive feedback loop in tumor cells. Increased lactate levels promoted M2 macrophage polarization, thereby inhibiting CD8 T cell activity.

Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.02] [4]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Resistant Drug: PD-1 mAb
• Molecule Alteration: Lactylation; H3K18la
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Immunocompetent mice inoculated with control Hepa1-6 cells; Mice
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: SRSF10 was upregulated in various tumors and associated with poor prognosis. Moreover, SRSF10 positively regulated lactate production, and SRSF10/glycolysis/ histone H3 lysine 18 lactylation (H3K18la) formed a positive feedback loop in tumor cells. Increased lactate levels promoted M2 macrophage polarization, thereby inhibiting CD8 T cell activity.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.02] [4]

• Metabolic Type: Glucose metabolism
• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Sensitive Drug: PD-1 mAb
• Molecule Alteration: Lactylation; H3K18la
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: ShSrsf10 Hepa1-6 cells into wild-type C57B/6 mice; Mice
• Experiment for Molecule Alteration: Western blot analysis
• Mechanism Description: SRSF10 was upregulated in various tumors and associated with poor prognosis. Moreover, SRSF10 positively regulated lactate production, and SRSF10/glycolysis/ histone H3 lysine 18 lactylation (H3K18la) formed a positive feedback loop in tumor cells. Increased lactate levels promoted M2 macrophage polarization, thereby inhibiting CD8 T cell activity.

Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.02] [4]

• Metabolic Type: Glucose metabolism
• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Sensitive Drug: PD-1 mAb
• Molecule Alteration: Lactylation; H3K18la
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Immunocompetent mice inoculated with shSrsf10 cells; Mice
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: SRSF10 was upregulated in various tumors and associated with poor prognosis. Moreover, SRSF10 positively regulated lactate production, and SRSF10/glycolysis/ histone H3 lysine 18 lactylation (H3K18la) formed a positive feedback loop in tumor cells. Increased lactate levels promoted M2 macrophage polarization, thereby inhibiting CD8 T cell activity.

Tamoxifen

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Breast adenocarcinoma [ICD-11: 2C60.1] [5]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Resistant Drug: Tamoxifen
• Molecule Alteration: Methylation; H3K36me2
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF7 cells; Breast; Homo sapiens (Human); CVCL_0031
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Apoptosis rate assay
• Mechanism Description: Mechanistically, TIGAR directly interacts with the antioxidant master regulator NRF2 and facilitates chromatin recruitment of NRF2, H3K4me3 methylase MLL1 and elongating Pol-II to stimulate the expression of both new (NSD2) and established (NQO1/2, PRDX1 and GSTM4) targets of NRF2, independent of its enzymatic activity. Nuclear TIGAR confers cancer cell resistance to chemotherapy and hormonal therapy in vitro and in tumors through effective maintenance of redox homeostasis. In addition, nuclear accumulation of TIGAR is positively associated with NSD2 expression in clinical tumors and strongly correlated with poor survival

Temozolomide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Glioblastoma [ICD-11: 2A00.02] [6]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Glioblastoma [ICD-11: 2A00.02]
• Resistant Drug: Temozolomide
• Molecule Alteration: Lactylation; H3K9la
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: TBD0220TR cells; Brain; Homo sapiens (Human); N.A.
• In Vitro Model: U87 cells; Brain; Homo sapiens (Human); CVCL_0022
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Apoptosis rate assay
• Mechanism Description: Lactylation is upregulated in recurrent glioblastoma (GBM) tissues and temozolomide (TMZ)-resistant cells, mainly concentrated in histone H3K9. H3K9 lactylation activates LUC7L2 transcription. LUC7L2 mediates MLH1 intron 7 retention to reduce MLH1 expression, thereby inhibit mismatch repair (MMR), ultimately leading to TMZ resistance.

Clinical Trial Drug(s) 1 drug(s) in total

Bafetinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Oral squamous cell carcinoma [ICD-11: 2B6E.0] [3]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Bafetinib
• Molecule Alteration: Lactylation; .
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: OSCC samples; Homo Sapiens
• Mechanism Description: We found that histone Kla-induced BCAM was overexpressed in OSCC, and a high BCAM level was related to a lower immune cell score and inhibition of immune response. On the other hand, BCAM induced EMT and angiogenesis, leading to OSCC malignant progression via activating the Notch signaling pathway. However, the difference of the BCAM function in Pan-cancers might be attributed to tumor heterogeneity. Taken together, BCAM played a vital role in OSCC chemotherapy resistance and prognosis and contributed to inhibition of the immune process, suggesting that it might be a novel therapeutic target for OSCC.

discontinued Drug(s) 1 drug(s) in total

Imexon

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Oral squamous cell carcinoma [ICD-11: 2B6E.0] [3]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Imexon
• Molecule Alteration: Lactylation; .
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: OSCC samples; Homo Sapiens
• Mechanism Description: We found that histone Kla-induced BCAM was overexpressed in OSCC, and a high BCAM level was related to a lower immune cell score and inhibition of immune response. On the other hand, BCAM induced EMT and angiogenesis, leading to OSCC malignant progression via activating the Notch signaling pathway. However, the difference of the BCAM function in Pan-cancers might be attributed to tumor heterogeneity. Taken together, BCAM played a vital role in OSCC chemotherapy resistance and prognosis and contributed to inhibition of the immune process, suggesting that it might be a novel therapeutic target for OSCC.

Investigative Drug(s) 1 drug(s) in total

Cisplatinum

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Oral squamous cell carcinoma [ICD-11: 2B6E.0] [3]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Cisplatinum
• Molecule Alteration: Lactylation; .
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: OSCC samples; Homo Sapiens
• Mechanism Description: We found that histone Kla-induced BCAM was overexpressed in OSCC, and a high BCAM level was related to a lower immune cell score and inhibition of immune response. On the other hand, BCAM induced EMT and angiogenesis, leading to OSCC malignant progression via activating the Notch signaling pathway. However, the difference of the BCAM function in Pan-cancers might be attributed to tumor heterogeneity. Taken together, BCAM played a vital role in OSCC chemotherapy resistance and prognosis and contributed to inhibition of the immune process, suggesting that it might be a novel therapeutic target for OSCC.

References

• Ref 1: 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 Jan;20(1):114-130.
• Ref 2: Single-cell transcriptome analysis reveals the association between histone lactylation and cisplatin resistance in bladder cancer. Drug Resist Updat. 2024 Mar;73:101059.
• Ref 3: Histone Lysine Lactylation (Kla)-induced BCAM Promotes OSCC Progression and Cis-Platinum Resistance. Oral Dis. 2025 Apr;31(4):1116-1132.
• Ref 4: Targeting SRSF10 might inhibit M2 macrophage polarization and potentiate anti-PD-1 therapy in hepatocellular carcinoma. Cancer Commun (Lond). 2024 Nov;44(11):1231-1260.
• Ref 5: Nuclear TIGAR mediates an epigenetic and metabolic autoregulatory loop via NRF2 in cancer therapeutic resistance. Acta Pharm Sin B. 2022 Apr;12(4):1871-1884.
• Ref 6: Histone H3K9 Lactylation Confers Temozolomide Resistance in Glioblastoma via LUC7L2-Mediated MLH1 Intron Retention. Adv Sci (Weinh). 2024 May;11(19):e2309290.