Pathogenic and Therapeutic Role of H3K4 Family of Methylases and Demethylases in Cancers

Kumar, Aman; Kumari, Niti; Nallabelli, Nayudu; Prasad, Rajendra

doi:10.1007/s12291-019-00828-x

Cited by 17 publications

(7 citation statements)

References 118 publications

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“…KMT2C serves as one of the key regulators of H3K4 methylation, and inactivation results in the development of ureteral neoplasms in mice. It has been reported in breast tumors, glioblastomas, melanoma, and pancreatic cancer in human patients [43][44][45]. Also referred to as MLL3, KMT2C is a component of the activating signal cointegrator complex, with overexpression documented in a number of epithelial neoplasms [44,46,47].…”

Section: Discussionmentioning

confidence: 99%

NGS Analysis Confirms Common TP53 and RB1 Mutations, and Suggests MYC Amplification in Ocular Adnexal Sebaceous Carcinomas

Peterson

Moore

Hicks

et al. 2021

IJMS

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Ocular adnexal (OA) sebaceous carcinomas generally demonstrate more aggressive clinical and histopathological phenotypes than extraocular cases, but the molecular drivers implicated in their oncogenesis remain poorly defined. A retrospective review of surgical and ocular pathology archives identified eleven primary resection specimens of OA sebaceous carcinomas with adequate tissue for molecular analysis; two extraocular cases were also examined. Next-generation sequencing was used to evaluate mutations and copy number changes in a large panel of cancer-associated genes. Fluorescence in situ hybridization (FISH) confirmed MYC copy number gain in select cases, and immunohistochemistry to evaluate MYC protein expression. The commonest mutations occurred in TP53 (10/13) and RB1 (7/13). Additional mutations in clinically actionable genes, or mutations with a frequency of at least 25%, included the NF1 (3/12), PMS2 (4/12), ROS1 (3/12), KMT2C (4/12), MNX1 (6/12), NOTCH1 (4/12), PCLO (3/12), and PTPRT (3/12) loci. Low level copy number gain suggestive of amplification of the MYC locus was seen in two cases, and confirmed using FISH. MYC protein expression, as assessed by immunohistochemistry, was present in almost all sebaceous carcinoma cases. Our findings support the concept that alterations in TP53 and RB1 are the commonest alterations in sebaceous carcinoma, and suggest that MYC may contribute to the oncogenesis of these tumors.

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Section: Discussionmentioning

confidence: 99%

NGS Analysis Confirms Common TP53 and RB1 Mutations, and Suggests MYC Amplification in Ocular Adnexal Sebaceous Carcinomas

Peterson

Moore

Hicks

et al. 2021

IJMS

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“…DPY30 also strongly influences tumorigenesis in several types of cancers (14)(15)(16). The knockdown or overexpression of DPY30 might directly regulate H3K4 methylation levels and significantly affect the ability of gastric cancer cells to proliferate, migrate and invade (6). DPY30 can also promote the expression of vimentin by regulating the H3K4 methylation level of the vimentin gene promoter, which promotes the epithelial-mesenchymal transition (EMT) in epithelial ovarian cancer (15).…”

Section: Identification and Validation Of Dpy30 As A Prognostic Bioma...mentioning

confidence: 99%

“…In mammalian cells, histone 3 lysine 4 (H3K4) methylation modifications are important for DNA methylation and epigenetic inheritance. H3K4, as a histone which codes or as an identifier of gene promoters, is closely associated with the cell cycle, DNA replication, cell proliferation, tumorigenesis, invasion metastasis and immune evasion in various malignant tumors (6). The agonist of H3K4 methylation depends on its core components [WD-repeat protein-5, retinoblastoma-binding…”

Section: Introductionmentioning

confidence: 99%

Identification and validation of DPY30 as a prognostic biomarker and tumor immune microenvironment infiltration characterization in esophageal cancer

et al. 2022

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Esophageal cancer (ESCA) is a lethal malignancy and is associated with the alterations of various genes and epigenetic modifications. The protein dpy-30 homolog (DPY30) is a core member of histone H3K4 methylation catalase and its dysfunction is associated with the occurrence and development of cancer. Therefore, the present study investigated the role of DPY30 in ESCA and evaluated the association between the expression of DPY30, the clinicopathological characteristics of ESCA and the tumor immune microenvironment. It conducted a comprehensive analysis of DPY30 in patients with ESCA using The Cancer Genome Atlas (TCGA) database and clinical tissue microarray specimens of ESCA. Immunohistochemistry was performed to assess the expression levels of DPY30 in tissues. Receiver operating curve analysis, Kaplan-Meier survival analysis and Cox regression analysis were performed to identify the diagnostic and prognostic value of DPY30. Gene Set Enrichment Analysis, protein-protein interaction network and Estimation of Stromal and Immune cells in Malignant Tumor tissues using the Expression data were used to screen DPY30-associated genes and evaluate the immune score of the TCGA samples. The results demonstrated that the expression of mRNA and protein levels of DPY30 were significantly upregulated in tumor tissues compared with normal tissue samples. The expression of DPY30 was closely associated with the poor prognosis of patients with ESCA. The present study also found that DPY30 expression and the pathological characteristics of ESCA were significantly correlated. Additionally, the expression of DPY30 demonstrated a significant positive correlation with various immune cells infiltration. The results suggested that DPY30 might influence tumor immune infiltration. In conclusion, the findings suggested that DPY30 might be a potential prognostic biomarker and an immunotherapeutic target in ESCA.

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“…However, the associated molecular mechanism remains to be established. H3K4 methylation (mono-, di-and tri-methylation) is catalysed by protein macrocomplexes that belong to the SET domain methyltransferase family [28,29]. These methyltransferases are categorised into subfamilies that include the Nuclear receptor binding SET Domain protein (NSD) subfamily, which comprises 3 members: NSD1, NSD2 (also known as WHSC1, for Wolf-Hirschhorn Syndrome candidate 1) and NSD3 (WHSC1L1 for WHSC1 protein Like 1).…”

Section: Introductionmentioning

confidence: 99%

The histone methyltransferase NSD3 contributes to sister chromatid cohesion and to cohesin loading at mitotic exit

Éot-Houllier

Magnaghi-Jaulin

Bourgine

et al. 2021

Preprint

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During the cell cycle, dynamic post-translational modifications modulate the association of the cohesin complex with chromatin. Phosphorylation / dephosphorylation and acetylation / deacetylation of histones and of cohesin components ensure correct establishment of cohesion during S phase and its proper dissolution during mitosis. In contrast, little is known about the contribution of methylation to the regulation of sister chromatid cohesion. We performed a RNA interference-mediated inactivation screen against 14 histone methyltransferases of the SET domain family that highlighted NSD3 as a factor essential for sister chromatid cohesion in mitosis. We established that NSD3 ensures proper level of the cohesin loader MAU2 and of cohesin itself onto chromatin at mitotic exit. Consistent with its implication in the loading of kollerin and cohesin complexes onto chromatin, we showed that NSD3 associates with chromatin in early anaphase prior to that of MAU2 and RAD21 and dissociates from chromatin upon cell’s entry into prophase. Finally, we demonstrated that of the two NSD3 variant that exist in somatic cells, the long form that carries the methyltransferase activity is the one that acts in cohesion regulation. Taken together, these results describe a novel factor associated with histone methylation in cohesin loading.

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Pathogenic and Therapeutic Role of H3K4 Family of Methylases and Demethylases in Cancers

Cited by 17 publications

References 118 publications

NGS Analysis Confirms Common TP53 and RB1 Mutations, and Suggests MYC Amplification in Ocular Adnexal Sebaceous Carcinomas

NGS Analysis Confirms Common TP53 and RB1 Mutations, and Suggests MYC Amplification in Ocular Adnexal Sebaceous Carcinomas

Identification and validation of DPY30 as a prognostic biomarker and tumor immune microenvironment infiltration characterization in esophageal cancer

The histone methyltransferase NSD3 contributes to sister chromatid cohesion and to cohesin loading at mitotic exit

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