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1.
Science ; 368(6497): 1314-1315, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32554584
2.
Anticancer Res ; 40(5): 2467-2474, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366390

RESUMO

BACKGROUND/AIM: The hormonally-active form of vitamin D, 1,25(OH)2D3, demonstrated activity against oral squamous cell carcinoma (OSCC). Cytochrome P450scc (CYP11A1)-derived vitamin D hydroxyderivatives, such as 20(OH)D3 and 1,20(OH)2D3, have overlapping beneficial effects with 1,25(OH)2D3 without causing hypercalcemia. This study sought to determine (i) whether 20(OH)D3 and 1,20(OH)2D3 exhibit antitumor effects against OSCC comparable to those of 1,25(OH)2D3 and (ii) whether these effects may stem from down-regulation of sonic hedgehog (SHH) or WNT/ß-catenin signaling pathways. MATERIALS AND METHODS: Effects on CAL-27 cells were assessed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt and spheroid assays. Signaling pathways were assessed by immunofluorescence and western blotting. RESULTS: 20(OH)D3 and 1,20(OH)2D3 inhibited the growth of CAL-27 and demonstrated inhibition of WNT/ß-catenin and the SHH signaling as evidenced by down-regulation of nuclear translocation of glioma-associated oncogene 1(GLI1) and ß-catenin. CONCLUSION: Noncalcemic vitamin D hydroxyderivatives demonstrated antitumor activities against OSCC comparable to those of 1,25(OH)2D3 Their activities against SHH and the WNT/ß-catenin pathways provide insight for a possible target for OSCC treatment.


Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/metabolismo , Proteínas Hedgehog/metabolismo , Neoplasias Bucais/metabolismo , Vitamina D/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Antineoplásicos/uso terapêutico , Biomarcadores , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Núcleo Celular , Imunofluorescência , Humanos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/etiologia , Neoplasias Bucais/patologia , Transporte Proteico , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Vitamina D/análogos & derivados , Vitamina D/uso terapêutico , beta Catenina/metabolismo
3.
Life Sci ; 253: 117736, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32360571

RESUMO

AIMS: Recently, studies indicated that inflammation could exacerbate the development of BC. Karyopherin α-2 (KPNA2) is a molecule which modulates nucleocytoplasmic transport and is involved in malignant cellular behavior and carcinogenesis. Our study aims to elucidate the role of KPNA2 in BC pathogenesis and explore the mechanism of KPNA2 in regulating inflammation-induced BC exacerbations. MAIN METHODS: We measured the expression of KPNA2 in BC cells. Through loss-of-function experiments, the functional role of KPNA2 in MCF-7 and MDA-MB-468 cells was evaluated. SK-BR-3 cells were treated with IL-6 as an inflammatory in vitro model of BC. ELISA determination exhibited the contents of cytokines. RANKL and leptomycin B treatments activated NF-κB signaling and inhibited the nuclear translocation of c-Myc, respectively. KEY FINDINGS: The results showed that KPNA2 was significantly up-regulated in BC and silencing KPNA2 inhibited the proliferation, migration and invasion of BC cells, while the cycle arrest was induced, via blocking NF-κB signaling and c-Myc nuclear translocation. IL-6 stimulated the secretions of IL-8 and IL-17 in BC cells, and elevated KPNA2 expression. However, KPNA2 knockdown suppressed the inflammatory responses and malignant progression of BC induced by IL-6. SIGNIFICANCE: In conclusion, our study illustrated that KPNA2 regulated BC development, as well as IL-6-induced inflammation and exacerbation, via NF-κB signaling and c-Myc nuclear translocation. This may provide a novel target for BC therapy.


Assuntos
Neoplasias da Mama/patologia , Inflamação/patologia , Interleucina-6/metabolismo , alfa Carioferinas/genética , Neoplasias da Mama/genética , Linhagem Celular , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Proliferação de Células/genética , Feminino , Técnicas de Silenciamento de Genes , Inativação Gênica , Humanos , Células MCF-7 , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transdução de Sinais , Regulação para Cima
5.
Int J Nanomedicine ; 15: 2583-2603, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368042

RESUMO

Introduction: Over the past several years, nano-based therapeutics were an effective cancer drug candidate in order to overcome the persistence of deadliest diseases and prevalence of multiple drug resistance (MDR). Methods: The main objective of our program was to design organosilane-modified Fe3O4/SiO2/APTS(~NH2) core magnetic nanocomposites with functionalized copper-Schiff base complex through the use of (3-aminopropyl)triethoxysilane linker as chemotherapeutics to cancer cells. The nanoparticles were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), field emission scanning electron microscopy (FE-SEM), TEM, and vibrating sample magnetometer (VSM) techniques. All analyses corroborated the successful synthesis of the nanoparticles. In the second step, all compounds of magnetic nanoparticles were validated as antitumor drugs through the conventional MTT assay against K562 (myelogenous leukemia cancer) and apoptosis study by Annexin V/PI and AO/EB. The molecular dynamic simulations of nanoparticles were further carried out; afterwards, the optimization was performed using MM+, semi-empirical (AM1) and Ab Initio (STO-3G), ForciteGemo Opt, Forcite Dynamics, Forcite Energy and CASTEP in Materials studio 2017. Results: The results showed that the anti-cancer activity was barely reduced after modifying the surface of the Fe3O4/SiO2/APTS nanoparticles with 2-hydroxy-3-methoxybenzaldehyde as Schiff base and then Cu(II) complex. The apoptosis study by Annexin V/PI and AO/EB stained cell nuclei was performed that apoptosis percentage of the nanoparticles increased upon increasing the thickness of Fe3O4 shell on the magnetite core. The docking studies of the synthesized compounds were conducted towards the DNA and Topoisomerase II via AutoDock 1.5.6 (The Scripps Research Institute, La Jolla, CA, USA). Conclusion: Results of biology activities and computational modeling demonstrate that nanoparticles were targeted drug delivery system in cancer treatment.


Assuntos
Cobre/química , Compostos Férricos/síntese química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Propilaminas/síntese química , Bases de Schiff/síntese química , Silanos/síntese química , Dióxido de Silício/síntese química , Apoptose , Núcleo Celular/metabolismo , DNA/química , DNA Topoisomerases Tipo II/química , Compostos Férricos/química , Humanos , Células K562 , Magnetismo , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestrutura , Propilaminas/química , Bases de Schiff/química , Silanos/química , Dióxido de Silício/química , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
6.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(1): 73-78, 2020 Jan 30.
Artigo em Chinês | MEDLINE | ID: mdl-32376550

RESUMO

OBJECTIVE: To investigate the association of chromosomal polymorphisms with multinucleated embryos in infertile couples undergoing in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI). METHODS: This retrospective case-control study was conducted among 1145 infertile couples undergoing their first IVF/ICSI cycles. According to their karyotype, the couples were divided into chromosomal polymorphism group and control group, and the former group was divided into 3 subgroups: inversion group, D and G genome polymorphic group and 1, 9, and 16 qh+group. The blastomere multinucleation rate, clinical pregnancy rate and live birth rate were compared between the groups. RESULTS: Of the total of 1145 couples, 139 (6.10%) had chromosomal polymorphisms at least in one partner. No significant differences were found in female age, BMI, basal FSH level, total gonadotropin dose, E2 level on day of HCG, number of oocytes retrieved, fertilization rate, top quality embryo rate, clinical pregnancy rate or live birth rate among the groups (P > 0.05). The multinuclear rate of the embryos in couples with pericentric inversion of chromosomes 1, 9, and Y chromosomes and those with D and G genome polymorphisms were 8.23% and 4.65%, respectively, significantly higher than that in the control group (2.69%; P < 0.05); the multinuclear rate of the embryos was 2.77% in 1, 9, and 16 qh+ group, similar with that in the control group (P > 0.05). CONCLUSIONS: Infertile couples with pericentric inversion of chromosomes 1, 9, and Y chromosomes and in those with D and G genome polymorphism are at higher risks of blastomere multinucleation in IVF- ICSI cycles; 1, 9, and 16 qh + polymorphisms do not increase the rate of blastomere multinucleation of the embryos.


Assuntos
Blastômeros , Núcleo Celular/patologia , Aberrações Cromossômicas , Injeções de Esperma Intracitoplásmicas , Estudos de Casos e Controles , Inversão Cromossômica , Desenvolvimento Embrionário , Feminino , Fertilização In Vitro , Humanos , Cariótipo , Masculino , Gravidez , Taxa de Gravidez , Estudos Retrospectivos
7.
Nat Cell Biol ; 22(4): 487-497, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32231307

RESUMO

During mouse embryonic development, pluripotent cells rapidly divide and diversify, yet the regulatory programs that define the cell repertoire for each organ remain ill-defined. To delineate comprehensive chromatin landscapes during early organogenesis, we mapped chromatin accessibility in 19,453 single nuclei from mouse embryos at 8.25 days post-fertilization. Identification of cell-type-specific regions of open chromatin pinpointed two TAL1-bound endothelial enhancers, which we validated using transgenic mouse assays. Integrated gene expression and transcription factor motif enrichment analyses highlighted cell-type-specific transcriptional regulators. Subsequent in vivo experiments in zebrafish revealed a role for the ETS factor FEV in endothelial identity downstream of ETV2 (Etsrp in zebrafish). Concerted in vivo validation experiments in mouse and zebrafish thus illustrate how single-cell open chromatin maps, representative of a mammalian embryo, provide access to the regulatory blueprint for mammalian organogenesis.


Assuntos
Cromatina/química , Células Endoteliais/metabolismo , Elementos Facilitadores Genéticos , Regulação da Expressão Gênica no Desenvolvimento , Organogênese/genética , Proteína 1 de Leucemia Linfocítica Aguda de Células T/genética , Animais , Linhagem da Célula/genética , Núcleo Celular/genética , Núcleo Celular/metabolismo , Cromatina/metabolismo , Embrião de Mamíferos , Embrião não Mamífero , Desenvolvimento Embrionário , Células Endoteliais/citologia , Perfilação da Expressão Gênica , Camundongos , Camundongos Transgênicos , Especificidade de Órgãos , Ligação Proteica , Análise de Célula Única , Proteína 1 de Leucemia Linfocítica Aguda de Células T/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcrição Genética , Peixe-Zebra , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
8.
Adv Exp Med Biol ; 1233: 263-277, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32274761

RESUMO

SUMO is a ubiquitin-like protein that covalently binds to lysine residues of target proteins and regulates many biological processes such as protein subcellular localization or stability, transcription, DNA repair, innate immunity, or antiviral defense. SUMO has a critical role in the signaling pathway governing type I interferon (IFN) production, and among the SUMOylation substrates are many IFN-induced proteins. The overall effect of IFN is increasing global SUMOylation, pointing to SUMO as part of the antiviral stress response. Viral agents have developed different mechanisms to counteract the antiviral activities exerted by SUMO, and some viruses have evolved to exploit the host SUMOylation machinery to modify their own proteins. The exploitation of SUMO has been mainly linked to nuclear replicating viruses due to the predominant nuclear localization of SUMO proteins and enzymes involved in SUMOylation. However, SUMOylation of numerous viral proteins encoded by RNA viruses replicating at the cytoplasm has been lately described. Whether nuclear localization of these viral proteins is required for their SUMOylation is unclear. Here, we summarize the studies on exploitation of SUMOylation by cytoplasmic RNA viruses and discuss about the requirement for nuclear localization of their proteins.


Assuntos
Citoplasma/virologia , Vírus de RNA/metabolismo , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Proteínas Virais/metabolismo , Núcleo Celular/metabolismo , Humanos , Sumoilação
10.
Life Sci ; 253: 117722, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32348834

RESUMO

AIMS: It is well known that pyruvate dehydrogenase kinase 1 (PDK1) is highly expressed in breast cancer (BC) tissues and promotes tumor growth, but the underlying mechanisms of this process are unclear. Here, we investigated the effects of nuclear PDK1 on growth, migration and invasion in human BC cells. MAIN METHODS: The sub-cellular localization of PDK1 in BC cells was performed with subcellular fractionation followed by Western blot and immunofluorescence. The localization of PDK1 in breast normal tissue and breast duct carcinoma was detected by Immunohistochemistry. Then the protein-protein interaction between PDK1 and Importin ß was verified by co-immunoprecipitation assay. Finally, the effects of nuclear PDK1 on cell proliferation, apoptosis, migration and invasion of BC cells were assessed. KEY FINDINGS: In addition to its well-known sub-cellular localization, PDK1 was present in the nucleus of BC cells, and EGF treatment increased nucleus distribution of PDK1. Moreover, the level of nuclear PDK1 accumulation facilitated the growth of BC cells. We also found that the entry of PDK1 into nucleus mainly relied on the nuclear localization signal (NLS), and NLS mutation inhibited the entry of PDK1 into nucleus; as a result, the migration and invasion abilities of BC cells were impaired, and the number of apoptotic cells was significantly increased. SIGNIFICANCE: Our findings provided a new supplement to the sub-cellular localization of PDK1 in BC cells and uncovered the function of nuclear PDK1 in facilitating BC cells growth, migration and invasion.


Assuntos
Apoptose/fisiologia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Quinase Piruvato Desidrogenase (Transferência de Acetil)/metabolismo , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Núcleo Celular/metabolismo , Proliferação de Células/fisiologia , Feminino , Humanos , Invasividade Neoplásica
11.
Mutat Res ; 850-851: 503147, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32247562

RESUMO

Bulbus Fritillariacirrhosa D. Don (BFC) has been widely used as an herbal medicament for respiratory diseases in China for over 2000 years. The ethnomedicinal effects of BFC have been scientifically verified, nevertheless its toxicity has not been completely studied. Previously, we have reported that the aqueous extract of BFC induces mitotic aberrations and chromosomal instability (CIN) in human colon epithelial NCM460 cells via dysfunctioning the mitotic checkpoint. Here, we extend this study and specifically focus on the influence of BFC on cytokinesis, the final step of cell division. One remarkable change in NCM460 cells following BFC treatment is the high incidence of binucleated cells (BNCs). More detailed investigation of the ana-telophases reveals that furrow ingression, the first stage of cytokinesis, is inhibited by BFC. Asynchronous cultures treatment demonstrates that furrow ingression defects induced by BFCs are highly associated with the formation of BNCs in ensuing interphase, indicating the BNCs phenotype after BFC treatment was resulted from cytokinesis failure. In line with this, the expression of genes involved in the regulation of furrow ingression is significantly de-regulated by BFC (e.g., LATS-1/2 and Aurora-B are upregulated, and YB-1 is downregulated). Furthermore, long-term treatment of BFC elucidates that the BNCs phenotype is transient and the loss of BNCs is associated with increased frequency of micronuclei and nuclear buds, two biomarkers of CIN. In supporting of these findings, the Nin Jiom Pei Pa Koa and Chuanbei Pipa Gao, two commercially available Chinese traditional medicines containing BFC, are able to induce multinucleation and CIN in NCM460 cells. Altogether, these data provide the first in vitro experimental evidence linking BFC to cytokinesis failure and suggest the resultant BNCs may be intermediates to produce CIN progenies.


Assuntos
Instabilidade Cromossômica/efeitos dos fármacos , Citocinese/efeitos dos fármacos , Fritillaria/química , Extratos Vegetais/farmacologia , Aurora Quinase B/genética , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/genética , Instabilidade Cromossômica/genética , Colo/efeitos dos fármacos , Colo/patologia , Citocinese/genética , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Mitose/efeitos dos fármacos , Extratos Vegetais/química , Raízes de Plantas/química , Proteínas Serina-Treonina Quinases/genética , Proteína 1 de Ligação a Y-Box/genética
16.
PLoS One ; 15(4): e0228760, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348304

RESUMO

Accurate RNA quantification at the single-cell level is critical for understanding the dynamics of gene expression and regulation across space and time. Single molecule FISH (smFISH), such as RNAscope, provides spatial and quantitative measurements of individual transcripts, therefore, can be used to explore differential gene expression among a heterogeneous cell population if combined with cell identify information. However, such analysis is not straightforward, and existing image analysis pipelines cannot integrate both RNA transcripts and cellular staining information to automatically output cell type-specific gene expression. We developed an efficient and customizable analysis method, Single-Molecule Automatic RNA Transcription Quantification (SMART-Q), to enable the analysis of gene transcripts in a cell type-specific manner. SMART-Q efficiently infers cell identity information from multiplexed immuno-staining and quantifies cell type-specific transcripts using a 3D Gaussian fitting algorithm. Furthermore, we have optimized SMART-Q for user experiences, such as flexible parameters specification, batch data outputs, and visualization of analysis results. SMART-Q meets the demands for efficient quantification of single-molecule RNA and can be widely used for cell type-specific RNA transcript analysis.


Assuntos
RNA/genética , Software , Transcrição Genética , Núcleo Celular/metabolismo , Humanos , Processamento de Imagem Assistida por Computador , Controle de Qualidade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
17.
Nat Struct Mol Biol ; 27(3): 260-273, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32123389

RESUMO

SRSF7 is an essential RNA-binding protein whose misexpression promotes cancer. Here, we describe how SRSF7 maintains its protein homeostasis in murine P19 cells using an intricate negative feedback mechanism. SRSF7 binding to its premessenger RNA promotes inclusion of a poison cassette exon and transcript degradation via nonsense-mediated decay (NMD). However, elevated SRSF7 levels inhibit NMD and promote translation of two protein halves, termed Split-ORFs, from the bicistronic SRSF7-PCE transcript. The first half acts as dominant-negative isoform suppressing poison cassette exon inclusion and instead promoting the retention of flanking introns containing repeated SRSF7 binding sites. Massive SRSF7 binding to these sites and its oligomerization promote the assembly of large nuclear bodies, which sequester SRSF7 transcripts at their transcription site, preventing their export and restoring normal SRSF7 protein levels. We further show that hundreds of human and mouse NMD targets, especially RNA-binding proteins, encode potential Split-ORFs, some of which are expressed under specific cellular conditions.


Assuntos
Regulação da Expressão Gênica , Proteínas de Neoplasias/genética , Fases de Leitura Aberta , Precursores de RNA/genética , Proteínas de Ligação a RNA/genética , Fatores de Processamento de Serina-Arginina/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Sítios de Ligação , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Núcleo Celular/ultraestrutura , Éxons , Homeostase/genética , Camundongos , Células-Tronco Embrionárias Murinas/citologia , Células-Tronco Embrionárias Murinas/metabolismo , Proteínas de Neoplasias/metabolismo , Degradação do RNAm Mediada por Códon sem Sentido , Ligação Proteica , Biossíntese de Proteínas , Precursores de RNA/metabolismo , Proteínas de Ligação a RNA/classificação , Proteínas de Ligação a RNA/metabolismo , Fatores de Processamento de Serina-Arginina/metabolismo , Transcrição Genética
18.
Plant Mol Biol ; 103(1-2): 197-210, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32130643

RESUMO

DEEPER ROOTING 1 (DRO1) contributes to the downward gravitropic growth trajectory of roots upstream of lateral auxin transport in monocots and dicots. Loss of DRO1 function leads to horizontally oriented lateral roots and altered gravitropic set point angle, while loss of all three DRO family members results in upward, vertical root growth. Here, we attempt to dissect the roles of AtDRO1 by analyzing expression, protein localization, auxin gradient formation, and auxin responsiveness in the atdro1 mutant. Current evidence suggests AtDRO1 is predominantly a membrane-localized protein. Here we show that VENUS-tagged AtDRO1 driven by the native AtDRO1 promoter complemented an atdro1 Arabidopsis mutant and the protein was localized in root tips and detectable in nuclei. atdro1 primary and lateral roots showed impairment in establishing an auxin gradient upon gravistimulation as visualized with DII-VENUS, a sensor for auxin signaling and proxy for relative auxin distribution. Additionally, PIN3 domain localization was not significantly altered upon gravistimulation in atdro1 primary and lateral roots. RNA-sequencing revealed differential expression of known root development-related genes in atdro1 mutants. atdro1 lateral roots were able to respond to exogenous auxin and AtDRO1 gene expression levels in root tips were unaffected by the addition of auxin. Collectively, the data suggest that nuclear localization may be important for AtDRO1 function and suggests a more nuanced role for DRO1 in regulating auxin-mediated changes in lateral branch angle. KEY MESSAGE: DEEPER ROOTING 1 (DRO1) when expressed from its native promoter is predominately localized in Arabidopsis root tips, detectable in nuclei, and impacts auxin gradient formation.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Raízes de Plantas/metabolismo , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Núcleo Celular/metabolismo , Teste de Complementação Genética , Gravitação , Mutação , Proteínas Nucleares/metabolismo
19.
PLoS Genet ; 16(3): e1008543, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32134927

RESUMO

Following fertilization of a mature oocyte, the formation of a diploid zygote involves a series of coordinated cellular events that ends with the first embryonic mitosis. In animals, this complex developmental transition is almost entirely controlled by maternal gene products. How such a crucial transcriptional program is established during oogenesis remains poorly understood. Here, we have performed an shRNA-based genetic screen in Drosophila to identify genes required to form a diploid zygote. We found that the Lid/KDM5 histone demethylase and its partner, the Sin3A-HDAC1 deacetylase complex, are necessary for sperm nuclear decompaction and karyogamy. Surprisingly, transcriptomic analyses revealed that these histone modifiers are required for the massive transcriptional activation of deadhead (dhd), which encodes a maternal thioredoxin involved in sperm chromatin remodeling. Unexpectedly, while lid knock-down tends to slightly favor the accumulation of its target, H3K4me3, on the genome, this mark was lost at the dhd locus. We propose that Lid/KDM5 and Sin3A cooperate to establish a local chromatin environment facilitating the unusually high expression of dhd, a key effector of the oocyte-to-zygote transition.


Assuntos
Proteínas de Drosophila/genética , Histona Desmetilases/genética , Oócitos/fisiologia , Zigoto/fisiologia , Animais , Núcleo Celular/genética , Cromatina/genética , Montagem e Desmontagem da Cromatina/genética , Drosophila/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento/genética , Histonas/genética , Masculino , Oogênese/genética , Espermatozoides/fisiologia , Transcrição Genética/genética
20.
Life Sci ; 250: 117547, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32173311

RESUMO

Gastric cancer (GC) is responsible for high morbidity and mortality worldwide. This cancer claims fifth place among other cancers. There are a number of factors associated with GC development such as alcohol consumption and tobacco smoking. It seems that genetic factors play significant role in GC malignancy and progression. MicroRNAs (miRs) are short non-coding RNA molecules with negative impact on the expression of target genes. A variety of studies have elucidated the potential role of miRs in GC growth. Investigation of molecular pathways has revealed that miRs function as upstream modulators of Wnt signaling pathway. This signaling pathway involves in important biological processes such as cell proliferation and differentiation, and its dysregulation is associated with GC invasion. At the present review, we demonstrate that how miRs regulate Wnt signaling pathway in GC malignancy.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Neoplasias Gástricas/metabolismo , Via de Sinalização Wnt , Apoptose , Diferenciação Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Núcleo Celular/metabolismo , Proliferação de Células , Citoplasma/metabolismo , Humanos , Ligantes , Transporte Proteico , Transdução de Sinais , Neoplasias Gástricas/patologia , beta Catenina/metabolismo
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