Dnmt3b catalytic activity is critical for its tumour suppressor function in lymphomagenesis and is associated with c-Met oncogenic signalling

Lopušná, Katarína; Nowialis, Pawel; Opavska, Jana; Abraham, Ajay; Riva, Alberto; Opavský, René

doi:10.1016/j.ebiom.2020.103191

Cited by 12 publications

(12 citation statements)

References 64 publications

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“…Although our data support the fact that such hypomethylation is due to a miR-539-5p-targeted decrease in DNMT3b levels and, consequently, of its activity, a contribution of its independent methyltransferase catalytic activity alone cannot be ruled out and needs further investigation, especially because, despite being dispensable, the catalytic activity of DNMT3b is critically associated with genomic elements that control tumorigenesis in mice by regulating processes involved in cellular transformation, including that of phosphatidylinositol 3-kinase (PI3K)-Akt, mitogen-activated kinase (MAPK), etc. 40 Srebf1 encodes a helix-loop-helix leucine zipper transcription factor, SREBP1, that binds to the sterol regulatory element primarily found . miR-539-5p administration improves hyperglycemia and normalizes miR-539-5p, Dnmt3b, and Srebf1 levels in skeletal muscle of diabetic db/db mice (A) Schematic of the experimental design for db/+ and db/db animals.…”

Section: Discussionmentioning

confidence: 99%

miR-539-5p regulates Srebf1 transcription in the skeletal muscle of diabetic mice by targeting DNA methyltransferase 3b

Kesharwani¹,

Kumar²,

Rizvi³

et al. 2022

Molecular Therapy - Nucleic Acids

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Section: Discussionmentioning

confidence: 99%

miR-539-5p regulates Srebf1 transcription in the skeletal muscle of diabetic mice by targeting DNA methyltransferase 3b

Kesharwani¹,

Kumar²,

Rizvi³

et al. 2022

Molecular Therapy - Nucleic Acids

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“…DNMT3B plays an important role in the differentiation of hematopoietic stem cells, embryo development and in some malignancies. There have been conflicting results from studies on its role either as a tumor suppressor or accelerator of progression in AML [14][15][16] . HDAC inhibitorinduced apoptosis in AML has been documented, and is consistent with our findings 17) .…”

Section: Discussionmentioning

confidence: 99%

The Impact of 6-Thioguanine on Epigenetics of Acute Myeloid Leukemia

Rostamian

Hekmatimoghaddam

Pourrajab

2021

Ann. Cancer Res. Therap.

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The drug 6-thioguanine (6-TG) is one of the thiopurines successfully used in oncology, especially for acute myeloid leukemia (AML). It is proposed to act as an epigenetic drug affecting DNA methylation. The aim of this study was to clarify the effect of 6-TG on the proliferation, viability and expression of genes coding for the enzymes DNA methyltransferase 3A and DNA methyltransferase 3B (DNMTs) as well as histone deacetylase 3 (HDAC3) and histone deacetylase 7 (HDAC7) in the human promyelocytic AML cell line HL60.In this experimental study, HL60 cells and also normal peripheral blood mononuclear cells (PBMCs) were grown in RPMI 1640 medium containing 10% fetal bovine serum. They were then treated with 6-TG at their exponential growth phase. Cell viability was monitored using the Cell Counting Kit-8 assay with an enzyme-linked immunosorbent assay (ELISA) reader. The expressions of the above mentioned 4 genes were quantified using real-time PCR.6-TG could inhibit the proliferation of HL60 cells and decrease their viability. In HL60 cells, as compared to normal PBMCs, 6-TG significantly decreased HDAC3 (p = 0.0034) as well as DNMT3B (p = 0.03) and HDAC7 (p = 0.0031) gene expressions, but increased the expression of DNMT3A gene (p = 0.16) after normalization to GAPDH as the housekeeping gene.These findings suggest that the altered expression of DNMT3A, DNMT3B, HDAC3 and HDAC7 genes is responsible for at least part of the antitumor properties of 6-TG, providing an insight into the mechanism of its action as an epigenetic drug.

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“…Expression of DNMT3B was decreased in iPSCs derived from KS1 patient (Carosso et al, 2019). Furthermore, Kdm6a and Chd7 have been reported to be interlinked in terms of gene expression regulation (Mansour et al, 2012;Hsu et al, 2020), and in a mouse model expressing catalytically inactive Dnmt3b, they share opposite behavior (Lopusna et al, 2021).…”

Section: Shared Epigenetic and Gene Expression Alterationsmentioning

confidence: 99%

“…In Table 2, shared pathways with genes deregulated by VPA and downregulated in models of causative genes for KLEFS, KS, CHARGE, MRD1, and ARTHS or ICF1 are summarized (Katsumoto et al, 2006;Issaeva et al, 2007;Min et al, 2007;Fan, 2008;Gupta-Agarwal et al, 2012;Mansour et al, 2012;Balemans et al, 2014;Chen et al, 2014;Kim et al, 2014;Schulz et al, 2014;Turner-Ivey et al, 2014;Gigek et al, 2015;Dhar et al, 2016Dhar et al, , 2018Fang et al, 2016;Mullegama et al, 2016;Sheikh et al, 2016Sheikh et al, , 2017Feng et al, 2017a,b;Shpargel et al, 2017;Whittaker et al, 2017;Baell et al, 2018;Marie et al, 2018;Yao et al, 2018Yao et al, , 2020Carosso et al, 2019;Machado et al, 2019;Nowialis et al, 2019;Cieslar-Pobuda et al, 2020;Frega et al, 2020;Hsu et al, 2020;Kong et al, 2020;Liu et al, 2020;Xu et al, 2020;Ying et al, 2020;Fei et al, 2021;Lopusna et al, 2021). Of note, the most commonly shared pathways involve either morphogenesis signals (for example, beta1 integrin cell surface interactions and extracellular matrix organization), or possible defects of the central nervous system (such as axon guidance and neuro...…”

Section: Shared Epigenetic and Gene Expression Alterationsmentioning

confidence: 99%

Chromatin Imbalance as the Vertex Between Fetal Valproate Syndrome and Chromatinopathies

Parodi

Fede

Peron

et al. 2021

Front. Cell Dev. Biol.

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Prenatal exposure to valproate (VPA), an antiepileptic drug, has been associated with fetal valproate spectrum disorders (FVSD), a clinical condition including congenital malformations, developmental delay, intellectual disability as well as autism spectrum disorder, together with a distinctive facial appearance. VPA is a known inhibitor of histone deacetylase which regulates the chromatin state. Interestingly, perturbations of this epigenetic balance are associated with chromatinopathies, a heterogeneous group of Mendelian disorders arising from mutations in components of the epigenetic machinery. Patients affected from these disorders display a plethora of clinical signs, mainly neurological deficits and intellectual disability, together with distinctive craniofacial dysmorphisms. Remarkably, critically examining the phenotype of FVSD and chromatinopathies, they shared several overlapping features that can be observed despite the different etiologies of these disorders, suggesting the possible existence of a common perturbed mechanism(s) during embryonic development.

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Dnmt3b catalytic activity is critical for its tumour suppressor function in lymphomagenesis and is associated with c-Met oncogenic signalling

Cited by 12 publications

References 64 publications

miR-539-5p regulates Srebf1 transcription in the skeletal muscle of diabetic mice by targeting DNA methyltransferase 3b

miR-539-5p regulates Srebf1 transcription in the skeletal muscle of diabetic mice by targeting DNA methyltransferase 3b

The Impact of 6-Thioguanine on Epigenetics of Acute Myeloid Leukemia

Chromatin Imbalance as the Vertex Between Fetal Valproate Syndrome and Chromatinopathies

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