Elevated DNA methylation in malignant tumors of the sinonasal tract and its association with patient survival

Chmelařová, Marcela; Laco, Ján; Kovaříková, Helena; Baranová, Ivana; Dundr, Pavel; Němejcová, Kristýna; Michálek, Jaroslav; Vošmik, Milan; Palička, Vladimír

doi:10.5507/bp.2018.012

Cited by 2 publications

(1 citation statement)

References 28 publications

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“…DNA methylation plays an important role in cancer biology, the down-regulation of certain genes due to methylation further affects the occurrence and development of tumors. [33][34][35] Methylation can chemically modify some proteins and nucleic acids to form methylated products. In biological system, methylation can regulate the expression of genes and the function of proteins.…”

Section: Discussionmentioning

confidence: 99%

Cyclophosphamide inhibits Pax5 methylation to regulate the growth of retinoblastoma via the Notch1 pathway

Jin

Lei

et al. 2021

Hum Exp Toxicol

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Retinoblastoma (Rb) is the most common intraocular malignant tumor in infants. Here, we investigated the function and mechanism of cyclophosphamide (CTX) in the development of Rb. Real-time quantitative polymerase chain reaction (RT-qPCR) results showed that paired box protein 5 (Pax5) expression was down-regulated in Rb tissues and cell lines. Methylation-specific PCR (MSP) results showed that the methylation level of Pax5 was up-regulated in Rb. After treatment with CTX, the Pax5 expression in Rb cell lines was increased significantly. The methylation of Pax5 and the expression of DNA methyltransferases (DNMTs) were down-regulated in the CTX group. Cyclophosphamide inhibited cell proliferation, migration, and invasion, promoted cell apoptosis via the Notch1 pathway. DNA methyltransferase inhibitor SGI-1027 had synergistic effects with CTX. Paired box protein 5 siRNA was transfected into Y79 cells treated with CTX. The expression of DNMTs, Pax5, the Notch1 pathway and apoptosis marker protein was detected by Western blotting, and changes in cell behavior were detected, respectively. Results showed that knockdown of Pax5 reversed the effects of CTX. Moreover, the Notch1 activator Valproic acid (VPA) abolished the inhibitory effects of CTX on Rb development. Moreover, CTX inhibited tumor growth in nude mice. These findings demonstrated that CTX up-regulated Pax5 expression by down-regulating DNMTs expression, and then inhibited the Notch1 signaling pathway activation and Rb growth.

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Section: Discussionmentioning

confidence: 99%

Cyclophosphamide inhibits Pax5 methylation to regulate the growth of retinoblastoma via the Notch1 pathway

Jin

Lei

et al. 2021

Hum Exp Toxicol

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DNA methylation and gene expression signatures are associated with ataxia-telangiectasia phenotype

McGrath‐Morrow¹,

Ndeh²,

Helmin

et al. 2020

Sci Rep

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People with ataxia-telangiectasia (A-T) display phenotypic variability with regard to progression of immunodeficiency, sino-pulmonary disease, and neurologic decline. To determine the association between differential gene expression, epigenetic state, and phenotypic variation among people with A-T, we performed transcriptional and genome-wide DNA methylation profiling in patients with mild and classic A-T progression as well as healthy controls. RNA and genomic DNA were isolated from peripheral blood mononuclear cells for transcriptional and DNA methylation profiling with RNA-sequencing and modified reduced representation bisulfite sequencing, respectively. We identified 555 genes that were differentially expressed among the control, mild A-T, and classic A-T groups. Genome-wide DNA methylation profiling revealed differential promoter methylation in cis with 146 of these differentially expressed genes. Functional enrichment analysis identified significant enrichment in immune, growth, and apoptotic pathways among the methylation-regulated genes. Regardless of clinical phenotype, all A-T participants exhibited downregulation of critical genes involved in B cell function (PAX5, CD79A, CD22, and FCRL1) and upregulation of several genes associated with senescence and malignancy, including SERPINE1. These findings indicate that gene expression differences may be associated with phenotypic variability and suggest that DNA methylation regulates expression of critical immune response genes in people with A-T.

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Elevated DNA methylation in malignant tumors of the sinonasal tract and its association with patient survival

Cited by 2 publications

References 28 publications

Cyclophosphamide inhibits Pax5 methylation to regulate the growth of retinoblastoma via the Notch1 pathway

Cyclophosphamide inhibits Pax5 methylation to regulate the growth of retinoblastoma via the Notch1 pathway

DNA methylation and gene expression signatures are associated with ataxia-telangiectasia phenotype

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