Epigenetic modifiers can alter telomerase expression and clonogenic capacities of Sézary cells

Epigenetics process is the heritable change in gene function that does not involve changes in the DNA sequence. Until now, several types of epigenetic mechanisms have been characterized, including DNA methylation, histone modification (acetylation, methylation, etc.), nucleosome remodeling, and noncoding RNAs. With the biological investigations of these modifiers, some of them are identified as promoters in the process of various diseases, such as cancer, cardiovascular disease and virus infection. Epigenetic changes may serve as potential “first hits” for tumorigenesis. Hence, targeting epigenetic modifiers is being considered as a promising way for disease treatment. To date, six agents in two epigenetic target classes (DNMT and HDAC) have been approved by the US Food and Drug Administration (FDA). Most of these drugs are applied in leukemia, lymphoma therapy, or are combined with other drugs for the treatment of solid tumor. Due to the rapid development of epigenetics and epigenetics targeted drugs, it is becoming an emerging area in targeted drug design.

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The Non-Canonical Aspects of MicroRNAs: Many Roads to Gene Regulation

Cells ◽

10.3390/cells8111465 ◽

2019 ◽

Vol 8 (11) ◽

pp. 1465 ◽

Cited By ~ 30

Author(s):

Christiaan J. Stavast ◽

Stefan J. Erkeland

Keyword(s):

Rna Polymerase Ii ◽

Transcriptional Activation ◽

Small Rnas ◽

Target Genes ◽

Biological Functions ◽

Rnase Iii ◽

Mrna Targets ◽

Argonaute Proteins ◽

Epigenetic Modifiers ◽

Encoding Genes

MicroRNAs (miRNAs) are critical regulators of gene expression. As miRNAs are frequently deregulated in many human diseases, including cancer and immunological disorders, it is important to understand their biological functions. Typically, miRNA-encoding genes are transcribed by RNA Polymerase II and generate primary transcripts that are processed by RNase III-endonucleases DROSHA and DICER into small RNAs of approximately 21 nucleotides. All miRNAs are loaded into Argonaute proteins in the RNA-induced silencing complex (RISC) and act as post-transcriptional regulators by binding to the 3′- untranslated region (UTR) of mRNAs. This seed-dependent miRNA binding inhibits the translation and/or promotes the degradation of mRNA targets. Surprisingly, recent data presents evidence for a target-mediated decay mechanism that controls the level of specific miRNAs. In addition, several non-canonical miRNA-containing genes have been recently described and unexpected functions of miRNAs have been identified. For instance, several miRNAs are located in the nucleus, where they are involved in the transcriptional activation or silencing of target genes. These epigenetic modifiers are recruited by RISC and guided by miRNAs to specific loci in the genome. Here, we will review non-canonical aspects of miRNA biology, including novel regulators of miRNA expression and functions of miRNAs in the nucleus.

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Blastic plasmacytoid dendritic cell neoplasm with genetic mutations in multiple epigenetic modifiers: a case report

Journal of International Medical Research ◽

10.1177/0300060520982667 ◽

2021 ◽

Vol 49 (2) ◽

pp. 030006052098266

Author(s):

Xinmei Dang ◽

Di Zhou ◽

Lingjun Meng ◽

Lintao Bi

Keyword(s):

Dendritic Cell ◽

Plasmacytoid Dendritic Cell ◽

Genetic Mutations ◽

Cell Surface Markers ◽

Targeted Therapeutics ◽

Genetic Studies ◽

Clinical Prognosis ◽

Epigenetic Modifiers ◽

Cell Neoplasm ◽

Underlying Pathogenesis

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive hematodermic malignancy derived from plasmacytoid dendritic cell precursors. Despite advances in our understanding of tumor cell surface markers, the pathogenesis of BPDCN remains largely unknown. No standard or optimal treatments are available for BPDCN, and the prognosis is usually poor. We report herein a case of BPDCN that harbored multiple genetic mutations in epigenetic modifiers such as TET2 and ZRSR2. Genetic studies in patients with BPDCN may provide insights into the underlying pathogenesis, prediction of clinical prognosis, and development of better targeted therapeutics for this rare clinical entity.

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Effects of Environmental Conditions on Nephron Number: Modeling Maternal Disease and Epigenetic Regulation in Renal Development

International Journal of Molecular Sciences ◽

10.3390/ijms22084157 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4157

Author(s):

Lars Fuhrmann ◽

Saskia Lindner ◽

Alexander-Thomas Hauser ◽

Clemens Höse ◽

Oliver Kretz ◽

...

Keyword(s):

Environmental Conditions ◽

High Glucose ◽

Culture Conditions ◽

Renal Development ◽

Organ Cultures ◽

Renal Growth ◽

Epigenetic Modifiers ◽

Metabolic Conditions ◽

Renal Size ◽

Maternal Disease

A growing body of evidence suggests that low nephron numbers at birth can increase the risk of chronic kidney disease or hypertension later in life. Environmental stressors, such as maternal malnutrition, medication and smoking, can influence renal size at birth. Using metanephric organ cultures to model single-variable environmental conditions, models of maternal disease were evaluated for patterns of developmental impairment. While hyperthermia had limited effects on renal development, fetal iron deficiency was associated with severe impairment of renal growth and nephrogenesis with an all-proximal phenotype. Culturing kidney explants under high glucose conditions led to cellular and transcriptomic changes resembling human diabetic nephropathy. Short-term high glucose culture conditions were sufficient for long-term alterations in DNA methylation-associated epigenetic memory. Finally, the role of epigenetic modifiers in renal development was tested using a small compound library. Among the selected epigenetic inhibitors, various compounds elicited an effect on renal growth, such as HDAC (entinostat, TH39), histone demethylase (deferasirox, deferoxamine) and histone methyltransferase (cyproheptadine) inhibitors. Thus, metanephric organ cultures provide a valuable system for studying metabolic conditions and a tool for screening for epigenetic modifiers in renal development.

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