Upregulation of DPY30 promotes cell proliferation and predicts a poor prognosis in cholangiocarcinoma

Hong, Zaifa; Zhang, Wenqing; Wang, Shuangjia; Li, Si-Yang; Shang, Jin; Fan, Li; Shen, Dong‐Yan

doi:10.1016/j.biopha.2019.109766

Cited by 12 publications

(17 citation statements)

References 28 publications

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“…36 STAT3 induces the downstream upregulation of the transcription factor FOXM1 (forkhead box protein M1), which is responsible for the aggressive phenotype of CCA cells cultured in high glucose. 37 Other pathways participate in the promotion of CCA growth in conditions of hyperglycaemia, including ROSmediated upregulation of chromodomain helicase DNA-binding protein 8 and mannosidase alpha class 2a member 2, 38 increased expression of DPY30 (a subunit of the SET1 and MLL family methyltransferase complexes), 39 the long noncoding RNA FAM66 40 and SIRT3-dependent activation of the HIF1a/PDK1/pyruvate dehydrogenase axis 41 (Fig. 1).…”

Section: Cca and Glucose Metabolismmentioning

confidence: 99%

Metabolic reprogramming in cholangiocarcinoma

Raggi

Taddei

Rae

et al. 2022

Journal of Hepatology

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Section: Cca and Glucose Metabolismmentioning

confidence: 99%

Metabolic reprogramming in cholangiocarcinoma

Raggi

Taddei

Rae

et al. 2022

Journal of Hepatology

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“…18 Accumulating evidence have revealed significant upregulation of DPY30 mRNA expression were observed in hepatocellular carcinoma, 28 cervical squamous cell carcinoma, 29 ovarian cancer, 19 and cholangiocarcinoma. 23 Our study showed that the mRNA level of DPY30 in melanoma was higher than in normal tissues. In addition, DPY30 could induce epithelial to mesenchymal transition by activating Wnt/β-catenin signaling in the progression of cervical squamous cell carcinoma.…”

Section: Discussionmentioning

confidence: 55%

“…The percentage of positive cells was scored as 0 (0-10%), 1 (10-25%), 2 (25-50%) or 3 (50-75%) or 4 (>75%). 23 DPY30 in nucleus was defined as negative (combined score from 0 to 6) or positive (combined score from 8 to 12). PD-L1 expression was considered positive when ≥5% membranous staining of tumor cells were positive, as described in previous studies.…”

Section: Tissue Microarray and Evaluation Of Immunostainingmentioning

confidence: 99%

The DPY30-H3K4me3 Axis-Mediated PD-L1 Expression in Melanoma

Zhang¹,

Han²,

Sun³

et al. 2022

JIR

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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.

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“…Owing to the critical role of DPY30 in maintaining H3K4 methylation, abnormal expression of DPY30 can lead to the initiation and progression of human diseases. Extensive studies have reported that DPY30 is overexpressed in many types of cancers, accompanied by increased H3K4me3 modification in cancer cells ( Dixit et al., 2022 ; Gu et al., 2021 ; He et al., 2019 ; Hong et al., 2020 ; Lee et al., 2015 ; Shah et al., 2019 ; Yang et al., 2018 ; Zhang et al., 2018 ). Overexpression of DPY30 promotes proliferation, migration, and invasion of tumor cells ( Lee et al., 2015 ; Yang et al., 2018 ; Zhang et al., 2018 ).…”

Section: Discussionmentioning

confidence: 99%