Related Experiment Video
Updated: Aug 27, 2025
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
The DPY30-H3K4me3 Axis-Mediated PD-L1 Expression in Melanoma
Zhichun Zhang1, Yixuan Han2, Qiuyue Sun1
1Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People's Republic of China.
Background:
DPY30 is a common subunit of the human SET1/MLL complex and is an essential protein required for the activity of SET1/MLL methyltransferase. DPY30 regulates the histone H3K4 modification, and dysfunction of DPY30 might contribute to the regulation of cancer immune evasion. However, the functions and regulation of DPY30 in the expression of programmed cell death ligand 1 (PD-L1) is still not completely explored.
Methods:
Various online databases were used for data processing and visualization, including UALCAN, Oncomine, cBioPortal, SangerBox, TISIDB, TIMER, and GEPIA databases. The expression of DPY30 and PD-L1 in melanoma tissues were evaluated by IHC. Chromatin Immunoprecipitation (ChIP), RT-PCR and flow cytometry were used to elucidate the underlying molecular mechanism of PD-L1 expression regulation and its function.
Results:
The mRNA level of DPY30 in melanoma was higher than in normal tissues. The expression of DPY30 was positively associated with TMB, neoantigens and PD-L1 expression. Furthermore, DPY30 expression showed significant positive correlations with immune suppressor cells and ICP genes involved in T-cell exhaustion. IHC showed that the positive rates of DPY30 and PD-L1 in melanoma tissues were 62% and 58%, respectively. Correlation analysis revealed that DPY30 over-expression was positively associated with PD-L1 expression. Silencing of DPY30 by specific siRNA significantly inhibited PD-L1 expression. ChIP analysis revealed that H3K4me3 levels were enriched in the proximal PD-L1 promoter region in tumor cells. Inhibition of DPY30 still suppressed the PD-L1 level in IFN-γ treated MMAC-SF cells. Furthermore, the apoptosis of PD1+ T-cells in co-culture with MMAC-SF cells by knockdown of DPY30 were markedly reduced.
Conclusion:
This study shows the roles of DPY30 in regulating the cancer immune evasion in melanoma. Targeting the DPY30-H3K4me3 axis might be an alternative approach to enhance the efficacy of checkpoint immunotherapy.
Insights
DPY30 protein levels are elevated in melanoma and correlate with PD-L1 expression, a key factor in immune evasion. Targeting DPY30 may enhance cancer immunotherapy effectiveness.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- DPY30 is a subunit of the SET1/MLL complex, regulating histone H3K4 methylation.
- DPY30 dysfunction is implicated in cancer immune evasion.
- The specific role of DPY30 in programmed cell death ligand 1 (PD-L1) expression remains underexplored.
Purpose of the Study:
- To investigate the role of DPY30 in regulating PD-L1 expression in melanoma.
- To elucidate the molecular mechanisms linking DPY30 to PD-L1 expression and cancer immunity.
Main Methods:
- Analysis of DPY30 and PD-L1 expression in melanoma using online databases (UALCAN, Oncomine, cBioPortal, SangerBox, TISIDB, TIMER, GEPIA) and immunohistochemistry (IHC).
- Chromatin Immunoprecipitation (ChIP), RT-PCR, and flow cytometry to determine the regulatory mechanism.
- DPY30 silencing using siRNA and co-culture assays with T-cells.
Main Results:
- DPY30 mRNA levels are higher in melanoma than normal tissues and positively correlate with tumor mutational burden (TMB), neoantigens, and PD-L1 expression.
- DPY30 expression is associated with immune suppressor cells and T-cell exhaustion markers.
- DPY30 overexpression correlates with PD-L1 expression in melanoma tissues (62% vs 58% positive rates).
- DPY30 silencing significantly reduces PD-L1 expression.
- ChIP assays show H3K4me3 enrichment at the PD-L1 promoter upon DPY30 inhibition.
- DPY30 inhibition reduces PD-L1 levels and decreases apoptosis of PD1+ T-cells.
Conclusions:
- DPY30 plays a significant role in regulating cancer immune evasion in melanoma by modulating PD-L1 expression.
- The DPY30-H3K4me3 axis is a potential therapeutic target to enhance checkpoint immunotherapy efficacy.
