Promoter-Specific Hypomethylation Is Associated with Overexpression of PLS3 , GATA6 , and TWIST1 in the Sezary Syndrome

Wong, Henry K.; Gibson, Heather M.; Hake, Timothy; Geyer, Susan; Frederickson, Julie; Marcucci, Guido; Caligiuri, Michael A.; Porcu, Pierluigi; Mishra, Anjali

doi:10.1038/jid.2015.116

Cited by 32 publications

(31 citation statements)

References 37 publications

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“…PLS3 is a kind of plastin protein expressed in a variety of organs, which is associated with various diseases (Sugimachi et al., ; Wong et al., ; Yanyan et al., ). The protein mainly functions in the dynamic assembly and disassembly of actin bundles (Tanaka‐Kamioka, Kamioka, Ris, & Lim, ).…”

Section: Discussionmentioning

confidence: 99%

A novel nonsense variant in PLS3 causes X‐linked osteoporosis in a Chinese family

Wang

Bian

Cheng

et al. 2019

Annals of Human Genetics

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Osteoporosis is a complex bone metabolic disorder. Genetic factors play an important role in the development of osteoporosis. Mutations in more than 15 genes have been identified to be responsible for osteoporosis to date. Most recently, the gene PLS3 encoding plastin 3 was recognized to be involved in X-linked osteoporosis. Here, we recruited a four-generation Chinese family with X-linked osteoporosis, which had its onset in childhood and was characterized by peripheral fractures and low bone mineral density. All affected individuals shared a nonsense variant (c.244C > T) in exon 4 of PLS3 on Xq23. The variant in affected individuals segregated with the osteoporosis phenotype. By restriction analysis using Dra I, this variant was confirmed in all affected individuals but was not detected in unaffected family members or in 100 unrelated Chinese male controls. The variant was predicted to cause a premature termination of messenger RNA (mRNA) translation (p.Gln82*). The mutant mRNA degraded via the mechanism of "nonsense-mediated mRNA decay." In the present study, we identified a novel nonsense variant of PLS3 in early-onset X-linked osteoporosis and provided a novel insight into the molecular mechanism underlying the pathogenesis of osteoporosis. K E Y W O R D Sc.244C > T, nonsense, PLS3, X-linked osteoporosis 92

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Section: Discussionmentioning

confidence: 99%

A novel nonsense variant in PLS3 causes X‐linked osteoporosis in a Chinese family

Wang

Bian

Cheng

et al. 2019

Annals of Human Genetics

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“…Analyses of the T cells in Sz patients and normal controls revealed particularly high selective expression of EphA4 and TWIST as well as in other types of CTCL (van Doorn et al, 2004). More recently, promoter DNA hypomethylation of TWIST has been associated with protein overexpression (Wong et al, 2015).…”

Section: Mt Inducers In T-cell Lymphomasmentioning

confidence: 99%

EMT‐ and MET‐related processes in nonepithelial tumors: importance for disease progression, prognosis, and therapeutic opportunities

2017

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The epithelial‐to mesenchymal (EMT) process is increasingly recognized for playing a key role in the progression, dissemination, and therapy resistance of epithelial tumors. Accumulating evidence suggests that EMT inducers also lead to a gain in mesenchymal properties and promote malignancy of nonepithelial tumors. In this review, we present and discuss current findings, illustrating the importance of EMT inducers in tumors originating from nonepithelial/mesenchymal tissues, including brain tumors, hematopoietic malignancies, and sarcomas. Among these tumors, the involvement of mesenchymal transition has been most extensively investigated in glioblastoma, providing proof for cell autonomous and microenvironment‐derived stimuli that provoke EMT‐like processes that regulate stem cell, invasive, and immunogenic properties as well as therapy resistance. The involvement of prominent EMT transcription factor families, such as TWIST, SNAI, and ZEB, in promoting therapy resistance and tumor aggressiveness has also been reported in lymphomas, leukemias, and sarcomas. A reverse process, resembling mesenchymal‐to‐epithelial transition (MET), seems particularly relevant for sarcomas, where (partial) epithelial differentiation is linked to less aggressive tumors and a better patient prognosis. Overall, a hybrid model in which more stable epithelial and mesenchymal intermediates exist likely extends to the biology of tumors originating from sources other than the epithelium. Deeper investigation and understanding of the EMT/MET machinery in nonepithelial tumors will shed light on the pathogenesis of these tumors, potentially paving the way toward the identification of clinically relevant biomarkers for prognosis and future therapeutic targets.

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“…It is widely accepted that promoter hypermethylation causes a downregulation of gene expression, whereas promoter hypomethylation is associated with the upregulation of gene expression1920. To understand if changes in promoter methylation affect gene transcription in PTC, we evaluated groups of genes that showed both differential methylation and expression between tumor and normal tissues.…”

Section: Resultsmentioning

confidence: 99%

CXCL12 methylation-mediated epigenetic regulation of gene expression in papillary thyroid carcinoma

Zhang

Wang

Chen

et al. 2017

Sci Rep

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Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, and its incidence rate is rapidly growing. It is necessary to understand the pathogenesis of PTC to develop effective diagnosis methods. Promoter methylation has been recognized to contribute to the alterations in gene expression observed in tumorigenesis. Our RNA-seq data identified 1191 differentially expressed mRNAs and 147 differentially expressed lncRNAs in PTC. Next, promoter methylation of these genes was detected by reduced representation bisulfite sequencing (RRBS) technology and comprehensively analyzed to identify differential methylation. In total, 14 genes (13 mRNAs and 1 lncRNA), in which methylation was intimately involved in regulating gene expression, were proposed as novel diagnostic biomarkers. To gain insights into the relationships among these 14 genes, a core co-function network was constructed based on co-expression, co-function and co-methylation data. Notably, CXCL12 was identified as an essential gene in the network that was closely connected with the other genes. These data suggested that CXCL12 down-regulation in PTC may be caused by promoter hypermethylation. Our study was the first to perform an RRBS analysis for PTC and suggested that CXCL12 may contribute to PTC development by methylation-mediated epigenetic regulation of gene expression.

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Promoter-Specific Hypomethylation Is Associated with Overexpression of PLS3 , GATA6 , and TWIST1 in the Sezary Syndrome

Cited by 32 publications

References 37 publications

A novel nonsense variant in PLS3 causes X‐linked osteoporosis in a Chinese family

A novel nonsense variant in PLS3 causes X‐linked osteoporosis in a Chinese family

EMT‐ and MET‐related processes in nonepithelial tumors: importance for disease progression, prognosis, and therapeutic opportunities

CXCL12 methylation-mediated epigenetic regulation of gene expression in papillary thyroid carcinoma

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