BACKGROUND: Recent developments regarding the contribution of microRNAs to tumor angiogenesis and the oncogenic effects of microRNAs point to their potential role in breast cancer angiogenesis. Tumor-derived exosomes are considered a rich source of microRNAs that can regulate the function of other cells in the tumor microenvironment, including vascular endothelial cells. This study analyzes the effect of tamoxifen chemotherapy on the expression of a key microRNA, miR-329, and introduces a regulatory link between this microRNA and the KDM1A gene associated with the vascular endothelial growth factor (VEGF) messaging pathway. MATERIALS AND METHODS: MCF-7 breast cancer cells were purchased and cultured in a complete culture medium. These cells were treated with tamoxifen and then their exosomes were extracted from the culture medium. The RNAs of the exosomes were isolated and the expression of miR-329, VEGF, and KDM1A genes in the exosomes was investigated using the real-time polymerase chain reaction (PCR) method. RESULTS: The results of this study showed that tamoxifen treatment increased the expression of miR-329 in exosomes derived from MCF-7 cancer cells. The expression of KDM1A and VEGF genes in drug-treated cell exosomes is downregulated. CONCLUSION: The results of this experiment demonstrated that the treatment of breast cancer cells with tamoxifen reduces the expression of VEGF and KDM1A by increasing miR-329. The treatment therefore reduces angiogenesis, and thus its anti-tumor effects are applied.

• Klíčová slova
• breast cancer,
• MeSH
• angiogeneze MeSH
• endoteliální buňky MeSH
• histondemethylasy MeSH
• lidé MeSH
• mikro RNA * genetika   MeSH
• nádorové mikroprostředí MeSH
• nádory prsu * farmakoterapie   genetika   MeSH
• tamoxifen farmakologie   MeSH
• vaskulární endoteliální růstový faktor A genetika   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• histondemethylasy MeSH
• KDM1A protein, human MeSH Prohlížeč
• mikro RNA * MeSH
• MIRN329 microRNA, human MeSH Prohlížeč
• tamoxifen MeSH
• vaskulární endoteliální růstový faktor A MeSH
• VEGFA protein, human MeSH Prohlížeč

Neurodevelopmental disorders (NDDs) result from highly penetrant variation in hundreds of different genes, some of which have not yet been identified. Using the MatchMaker Exchange, we assembled a cohort of 27 individuals with rare, protein-altering variation in the transcriptional coregulator ZMYM3, located on the X chromosome. Most (n = 24) individuals were males, 17 of which have a maternally inherited variant; six individuals (4 male, 2 female) harbor de novo variants. Overlapping features included developmental delay, intellectual disability, behavioral abnormalities, and a specific facial gestalt in a subset of males. Variants in almost all individuals (n = 26) are missense, including six that recurrently affect two residues. Four unrelated probands were identified with inherited variation affecting Arg441, a site at which variation has been previously seen in NDD-affected siblings, and two individuals have de novo variation resulting in p.Arg1294Cys (c.3880C>T). All variants affect evolutionarily conserved sites, and most are predicted to damage protein structure or function. ZMYM3 is relatively intolerant to variation in the general population, is widely expressed across human tissues, and encodes a component of the KDM1A-RCOR1 chromatin-modifying complex. ChIP-seq experiments on one variant, p.Arg1274Trp, indicate dramatically reduced genomic occupancy, supporting a hypomorphic effect. While we are unable to perform statistical evaluations to definitively support a causative role for variation in ZMYM3, the totality of the evidence, including 27 affected individuals, recurrent variation at two codons, overlapping phenotypic features, protein-modeling data, evolutionary constraint, and experimentally confirmed functional effects strongly support ZMYM3 as an NDD-associated gene.

• Klíčová slova
• X-linked intellectual disability, ZMYM3, chromatin modifiers, neurodevelopmental disorder, transcriptional coregulators,
• MeSH
• fenotyp MeSH
• histondemethylasy genetika   MeSH
• jaderné proteiny genetika   MeSH
• lidé MeSH
• malformace nervového systému * MeSH
• mentální retardace * genetika   MeSH
• neurovývojové poruchy * genetika   MeSH
• obličej MeSH
• regulace genové exprese MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• histondemethylasy MeSH
• jaderné proteiny MeSH
• KDM1A protein, human MeSH Prohlížeč
• ZMYM3 protein, human MeSH Prohlížeč

The nuclear periphery (NP) plays a substantial role in chromatin organization. Heterochromatin at the NP is interspersed with active chromatin surrounding nuclear pore complexes (NPCs); however, details of the peripheral chromatin organization are missing. To discern the distribution of epigenetic marks at the NP of HeLa nuclei, we used structured illumination microscopy combined with a new MATLAB software tool for automatic NP and NPC detection, measurements of fluorescent intensity and statistical analysis of measured data. Our results show that marks for both active and non-active chromatin associate differentially with NPCs. The incidence of heterochromatin marks, such as H3K27me2 and H3K9me2, was significantly lower around NPCs. In contrast, the presence of marks of active chromatin such as H3K4me2 was only decreased very slightly around the NPCs or not at all (H3K9Ac). Interestingly, the histone demethylases LSD1 (also known as KDM1A) and KDM2A were enriched within the NPCs, suggesting that there was a chromatin-modifying mechanism at the NPCs. Inhibition of transcription resulted in a larger drop in the distribution of H1, H3K9me2 and H3K23me2, which implies that transcription has a role in the organization of heterochromatin at the NP.

• Klíčová slova
• Chromatin, Histone modification, Image analysis, Nuclear pore complexes, Nucleus, Structured illumination microscopy,
• MeSH
• buněčné jádro metabolismus   MeSH
• chromatin chemie   metabolismus   MeSH
• epigeneze genetická MeSH
• fluorescenční mikroskopie MeSH
• HeLa buňky MeSH
• heterochromatin chemie   MeSH
• histondemethylasy metabolismus   MeSH
• histony chemie   MeSH
• jaderný obal metabolismus   MeSH
• jaderný pór metabolismus   MeSH
• lidé MeSH
• mikroskopie metody   MeSH
• software MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chromatin MeSH
• heterochromatin MeSH
• histondemethylasy MeSH
• histony MeSH
• KDM1A protein, human MeSH Prohlížeč

Multiple myeloma (MM) is a hematological malignancy caused by the clonal expansion of plasma cells. The incidence of MM worldwide is increasing with greater than 140 000 people being diagnosed with MM per year. Whereas 5-year survival after a diagnosis of MM has improved from 28% in 1975 to 56% in 2012, the disease remains essentially incurable. In this review, we summarize our current understanding of MM including its epidemiology, genetics and biology. We will also provide an overview of MM management that has led to improvements in survival, including recent changes to diagnosis and therapies. Areas of unmet need include the management of patients with high-risk MM, those with reduced performance status and those refractory to standard therapies. Ongoing research into the biology and early detection of MM as well as the development of novel therapies, such as immunotherapies, has the potential to influence MM practice in the future.

• Klíčová slova
• clinical presentation, plasma cell disease, risks factors, survival, treatment,
• MeSH
• cyklin D1 genetika   MeSH
• exozom genetika   MeSH
• genetická predispozice k nemoci MeSH
• histondemethylasy genetika   MeSH
• imunoterapie metody   MeSH
• lidé MeSH
• míra přežití MeSH
• mnohočetný myelom diagnóza   epidemiologie   genetika   terapie   MeSH
• mutace MeSH
• nádorové biomarkery genetika   MeSH
• plazmatické buňky imunologie   patologie   MeSH
• represorové proteiny genetika   MeSH
• rizikové faktory MeSH
• transkripční elongační faktory genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• CCND1 protein, human MeSH Prohlížeč
• CDCA7L protein, human MeSH Prohlížeč
• cyklin D1 MeSH
• DIS3 protein, human MeSH Prohlížeč
• ELL2 protein, human MeSH Prohlížeč
• exozom MeSH
• histondemethylasy MeSH
• KDM1A protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• represorové proteiny MeSH
• transkripční elongační faktory MeSH