The activatory long non-coding RNA DBE-T reveals the epigenetic etiology of facioscapulohumeral muscular dystrophy

Vizoso, Miguel; Esteller, Manel

doi:10.1038/cr.2012.93

Cited by 17 publications

(8 citation statements)

References 11 publications

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“…37 ASH1 L mediates the dimethylation of H3K36 and trimethylation of H3K4. 38 While methylation of H3K4 mediated by ASH1 L was found to be crucial in the global-genome nucleotide excision repair activity to prevent ultraviolet light-induced skin cancer, 39 the ASH1L-mediated dimethylation mark of H3K36 could be recognized by LEDGF to recruit mixed-lineage leukemia (MLL)-associated proteins to activate gene expression of principle targets in leukemia cells, the process of which could be specifically antagonized by KDM2A, the demethylation of H3K36. 40 Therefore, the interactions of ASH1L-LEDGF-KDM2A were considered crucial underlying the tumorigenesis of MLL-associated leukemia.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Bioinformatics Analysis of Key Methyltransferases and Demethylases for Histone Lysines in Hepatocellular Carcinoma

Yang

Tang

Chen

et al. 2020

Technol Cancer Res Treat

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Background & Aims: Methylation of lysines on histones, controlled by various methyltransferases and demethylases, is an important component of epigenetic modifications, and abnormal regulation of such enzymes serves as common events in hepatocellular carcinoma. We determined to identify important methyltransferases and demethylases that might regulate the development of hepatocellular carcinoma by bioinformatics. Methods: The Oncomine and UALCAN databases were used to retrieve mRNA expression levels of histone lysine methyltransferases and demethylases in hepatocellular carcinoma. Data analyses of genetic alterations, mainly mutations and copy number alterations, were performed on the cBioportal platform. Protein-protein interactions were established in the STRING database. Results: mRNA expression of 8 genes correlated with clinical staging and grading, whereas 4 genes indicated a role in the prognosis, all co-expressed with SEDB1 and WHSC1. Genetically, 12 genes showing an alteration rate higher than 5% were identified, and only 3 were indicative of prognosis. Copy number gains in ASH1L, SETDB1, and KDM5B might partially contribute to the upregulation of their mRNA expression. The close relationship of mutations in MLL2/MLL3 with driver gene mutations in hepatocellular carcinoma provided a rationale for further investigation. Conclusions: We identified 11 methyltransferases and demethylases for major histone lysines that might be promising research targets in the pathogenesis, development, and prediction of prognosis in hepatocellular carcinoma using bioinformatics.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Bioinformatics Analysis of Key Methyltransferases and Demethylases for Histone Lysines in Hepatocellular Carcinoma

Yang

Tang

Chen

et al. 2020

Technol Cancer Res Treat

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“…In particular, DBE-T, whose gene is localized near the D4Z4 array, can be considered the better-known chromatin-associated lnc-RNA involved in the topological reorganization of the D4Z4 array. The lnc-RNA DBE-T was detected in FSHD primary muscle cells and biopsies, and it was found to contribute to the local transcriptional derepression by recruiting chromatin activators [ 46 , 47 ].…”

Section: Epigenetic Features Of Fshdmentioning

confidence: 99%

Update on the Molecular Aspects and Methods Underlying the Complex Architecture of FSHD

Caputo

Megalizzi

Fabrizio

et al. 2022

Cells

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Despite the knowledge of the main mechanisms involved in facioscapulohumeral muscular dystrophy (FSHD), the high heterogeneity and variable penetrance of the disease complicate the diagnosis, characterization and genotype–phenotype correlation of patients and families, raising the need for further research and data. Thus, the present review provides an update of the main molecular aspects underlying the complex architecture of FSHD, including the genetic factors (related to D4Z4 repeated units and FSHD-associated genes), epigenetic elements (D4Z4 methylation status, non-coding RNAs and high-order chromatin interactions) and gene expression profiles (FSHD transcriptome signatures both at bulk tissue and single-cell level). In addition, the review will also describe the methods currently available for investigating the above-mentioned features and how the resulting data may be combined with artificial-intelligence-based pipelines, with the purpose of developing a multifunctional tool tailored to enhancing the knowledge of disease pathophysiology and progression and fostering the research for novel treatment strategies, as well as clinically useful biomarkers. In conclusion, the present review highlights how FSHD should be regarded as a disease characterized by a molecular spectrum of genetic and epigenetic factors, whose alteration plays a differential role in DUX4 repression and, subsequently, contributes to determining the FSHD phenotype.

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“…LncDBET (ENST00000630918) is the transcript of the D4Z4 binding element. It was first reported in facioscapulohumeral muscular dystrophy (FSHD), where it regulates 4q35 chromatin structure and gene derepression to cause disease 37 , 38 . Nevertheless, there has been inadequate research on lncDBET in human cancers.…”

Section: Discussionmentioning

confidence: 99%

m⁶A-induced lncDBET promotes the malignant progression of bladder cancer through FABP5-mediated lipid metabolism

Liu¹,

Fan²,

Othmane³

et al. 2022

Theranostics

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The limited effect of adjuvant therapy for advanced bladder cancer (BCa) leads to a poor prognosis. Increasing evidence has shown that RNA N6-methyladenosine (m 6 A) modification plays important functional roles in tumorigenesis. Nevertheless, the role and mechanism of m6A-modified noncoding RNAs (ncRNAs) in BCa remain largely unknown. Methods: RT-PCR, western blotting and ONCOMINE dataset were used to determine the dominant m 6 A-related enzyme in BCa. M 6 A-lncRNA epitranscriptomic microarray was used to screen candidate targets of METTL14. RT-PCR, MeRIP and TCGA dataset were carried out to confirm the downstream target of METTL14. CHIRP/MS was conducted to identify the candidate proteins binding to lncDBET. RT-PCR, western blotting, RIP and KEGG analysis were used to confirm the target of lncDBET. The levels of METTL14, lncDBET and FABP5 were tested in vitro and in vivo . CCK-8, EdU, transwell and flow cytometry assays were performed to determine the oncogenic function of METTL14, lncDBET and FABP5, and their regulatory networks. Results : We identified that the m 6 A level of total RNA was elevated and that METTL14 was the dominant m6A-related enzyme in BCa. m 6 A modification mediated by METTL14 promoted the malignant progression of BCa by promoting the expression of lncDBET. Upregulated lncDBET activated the PPAR signalling pathway to promote the lipid metabolism of cancer cells through direct interaction with FABP5, thus promoting the malignant progression of BCa in vitro and in vivo . Conclusions : Our study establishes METTL14/lncDBET/FABP5 as a critical oncogenic axis in BCa.

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The activatory long non-coding RNA DBE-T reveals the epigenetic etiology of facioscapulohumeral muscular dystrophy

Cited by 17 publications

References 11 publications

Comprehensive Bioinformatics Analysis of Key Methyltransferases and Demethylases for Histone Lysines in Hepatocellular Carcinoma

Comprehensive Bioinformatics Analysis of Key Methyltransferases and Demethylases for Histone Lysines in Hepatocellular Carcinoma

Update on the Molecular Aspects and Methods Underlying the Complex Architecture of FSHD

m⁶A-induced lncDBET promotes the malignant progression of bladder cancer through FABP5-mediated lipid metabolism

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The activatory long non-coding RNA DBE-T reveals the epigenetic etiology of facioscapulohumeral muscular dystrophy

Cited by 17 publications

References 11 publications

Comprehensive Bioinformatics Analysis of Key Methyltransferases and Demethylases for Histone Lysines in Hepatocellular Carcinoma

Comprehensive Bioinformatics Analysis of Key Methyltransferases and Demethylases for Histone Lysines in Hepatocellular Carcinoma

Update on the Molecular Aspects and Methods Underlying the Complex Architecture of FSHD

m6A-induced lncDBET promotes the malignant progression of bladder cancer through FABP5-mediated lipid metabolism

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m⁶A-induced lncDBET promotes the malignant progression of bladder cancer through FABP5-mediated lipid metabolism