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1.
FASEB J ; : fj201700715, 2018 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-29920222

RESUMEN

Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality globally. Although cigarette smoking is by far the most important risk factor for lung cancer, the aberrant expression of oncogenes and tumor suppressor genes contributes a great deal to tumorigenesis. Here, we reveal that aberrant expression of endothelial PAS domain-containing protein 1 ( EPAS1) gene, which encodes hypoxia inducible factor 2α, has a critical role in NSCLC. Our results showed EPAS1 mRNA was down-regulated in 82.5% of NSCLC tissues, and a new region of EPAS1 promoter was found to be highly methylated in lung cancer cell lines and NSCLC tissues. Moreover, the methylation rates were negatively correlated to EPAS1 mRNA expression in lung tissues. Further, demethylation analysis demonstrated EPAS1 was regulated by DNA methyltransferases (DNMTs) in NSCLC. In contrast, DNMT1 was verified as an EPAS1 target gene by chromatin immunoprecipitation assay and could be transactivated by stabilized EPAS1 proteins in hypoxic lung cells, thereby decreasing EPAS1 mRNA expression by methylation regulation. Collectively, our study suggests there might be a mechanism of negative-feedback regulation for EPAS1 in NSCLC. That is, hypoxic-stabilized EPAS1 proteins transactivated DNMT1, which further promoted the hypermethylation of EPAS1 promoter and decreased EPAS1 mRNA expression levels in NSCLC.-Xu, X.-H., Bao, Y., Wang, X., Yan, F., Guo, S., Ma, Y., Xu, D., Jin, L., Xu, J., Wang, J. Hypoxic-stabilized EPAS1 proteins transactivate DNMT1 and cause promoter hypermethylation and transcription inhibition of EPAS1 in non-small cell lung cancer.

2.
Glycoconj J ; 32(8): 559-74, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26239924

RESUMEN

This review summarises the literature on the synthesis and applications of fluorescently labelled carbohydrates. Due to the sensitivity of fluorescent detection, this approach provides a useful tool to study processes involving glycans. A few general categories of labelling are presented, in situ labelling of carbohydrates with fluorophores, fluorescently labelled glycolipids, fluorogenic glycans, pre-formed fluorescent glycans for intracellular applications, glycan-decorated fluorescent polymers, fluorescent glyconanoparticles, and other functional fluorescent glycans.


Asunto(s)
Carbohidratos/química , Colorantes Fluorescentes/química , Nanopartículas/química , Polisacáridos/química , Animales , Bacterias/metabolismo , Compuestos de Boro/química , Ácidos Borónicos/química , Glucolípidos/química , Glicósidos/química , Humanos , Iones , Lectinas/química , Ratones , Polímeros/química
3.
FASEB J ; 27(10): 4194-203, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23804241

RESUMEN

Deregulation of promyelocytic leukemia zinc finger protein (PLZF), a tumor suppressor gene, was reported in different types of solid tumors. This study for the first time explored the reduced expression of PLZF and its effects in non-small-cell lung cancer (NSCLC) carcinogenesis. PLZF was found to be down-regulated by 62.8% in 87.1% of 154 paired NSCLC samples by quantitative real-time PCR, and its expression was found to be associated with the sex of the patient (P=0.02). Further analysis showed that down-regulation of PLZF in 35.6% NSCLC samples (31 out of 87) was triggered by hypermethylation in the promoter region. This was validated by demethylation analysis using the A549 cell line. Dual-luciferase reporter assay indicated that CTCF binding to the promoter region could activate PLZF transcription. Overexpression of PLZF in both A549 and LTEP lung cancer cell lines was found to inhibit proliferation and increase apoptosis. Therefore, reduced expression of PLZF was found to be common in NSCLC. PLZF down-regulation was partially correlated with hypermethylation in the promoter region. Decreased levels of PLZF expression may contribute to the pathogenesis of NSCLC by promoting cell survival. Therefore, the restoration of PLZF expression may serve as a new strategy for NSCLC therapy.


Asunto(s)
Apoptosis/fisiología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Proliferación Celular , Regulación Neoplásica de la Expresión Génica/fisiología , Factores de Transcripción de Tipo Kruppel/metabolismo , Factor de Unión a CCCTC , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular Tumoral , Femenino , Humanos , Factores de Transcripción de Tipo Kruppel/genética , Masculino , Persona de Mediana Edad , Regiones Promotoras Genéticas , Proteína de la Leucemia Promielocítica con Dedos de Zinc , Proteínas Represoras/genética , Proteínas Represoras/metabolismo
4.
ACS Med Chem Lett ; 12(9): 1486-1492, 2021 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-34531957

RESUMEN

A significant proportion of genetic disease cases arise from truncation of proteins caused by premature termination codons. In eukaryotic cells some aminoglycosides cause readthrough of premature termination codons during protein translation. Inducing readthrough of these codons can potentially be of therapeutic value in the treatment of numerous genetic diseases. A significant drawback to the repeated use of aminoglycosides as treatments is the lack of balance between their readthrough efficacy and toxicity. The synthesis and biological testing of designer aminoglycoside compounds is documented herein. We disclose the implementation of a strategy to reduce cellular toxicity and maintain readthrough activity of a library of compounds by modification of the overall cationic charge of the aminoglycoside scaffold through ring I modifications.

5.
Carbohydr Res ; 424: 15-20, 2016 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-26918516

RESUMEN

BODIPY fluorophores bearing azide or terminal alkyne functions were conjugated with glycans modified with terminal alkyne or azido through the Cu(I)-catalyzed 1,3-dipolar azide-alkyne cycloaddition (CuAAC) chemistry under microwave heating while these reactions did not proceed when heated in an oil-bath. The BODIPY-glycan conjugate product 8a undergoes self-assembly into liposomes when hydrated. Formation of liposomes was confirmed by both bright field and confocal microscopy. Fluorescent emission within the liposome was shifted from green to red due to effective high concentrations.


Asunto(s)
Compuestos de Boro/química , Liposomas/ultraestructura , Polisacáridos/química , Química Clic , Liposomas/química , Microscopía Confocal
6.
Clin Epigenetics ; 7: 3, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25657825

RESUMEN

BACKGROUND: DNA methylation was suggested as the promising biomarker for lung cancer diagnosis. However, it is a great challenge to search for the optimal combination of methylation biomarkers to obtain maximum diagnostic performance. RESULTS: In this study, we developed a panel of DNA methylation biomarkers and validated their diagnostic efficiency for non-small cell lung cancer (NSCLC) in a large Chinese Han NSCLC retrospective cohort. Three high-throughput DNA methylation microarray datasets (458 samples) were collected in the discovery stage. After normalization, batch effect elimination and integration, significantly differentially methylated genes and the best combination of the biomarkers were determined by the leave-one-out SVM (support vector machine) feature selection procedure. Then, candidate promoters were examined by the methylation status determined single nucleotide primer extension technique (MSD-SNuPET) in an independent set of 150 pairwise NSCLC/normal tissues. Four statistical models with fivefold cross-validation were used to evaluate the performance of the discriminatory algorithms. The sensitivity, specificity and accuracy were 86.3%, 95.7% and 91%, respectively, in Bayes tree model. The logistic regression model incorporated five gene methylation signatures at AGTR1, GALR1, SLC5A8, ZMYND10 and NTSR1, adjusted for age, sex and smoking, showed robust performances in which the sensitivity, specificity, accuracy, and area under the curve (AUC) were 78%, 97%, 87%, and 0.91, respectively. CONCLUSIONS: In summary, a high-throughput DNA methylation microarray dataset followed by batch effect elimination can be a good strategy to discover optimal DNA methylation diagnostic panels. Methylation profiles of AGTR1, GALR1, SLC5A8, ZMYND10 and NTSR1, could be an effective methylation-based assay for NSCLC diagnosis.

7.
J Org Chem ; 68(6): 2426-31, 2003 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-12636412

RESUMEN

A practical sequence is described for converting d-glucosamine into peracetylated Gal(beta-1,4)GlcNTroc(beta1-S)Ph and Neu5Ac(alpha-2,3)Gal(beta-1,4)GlcNTroc(beta1-S)Ph building blocks using a synthetic strategy based on chemoenzymatic oligosaccharide synthesis. The known trichloroethoxycarbonyl, N-Troc, protecting group was selected as a suitable protecting group for both enzymatic and chemical reaction conditions. These oligosaccharide building blocks proved effective donors for the beta-selective glycosylation of the unreactive OH-3 of a polymeric PEG-bound acceptor and for the axial OH-2 of a mannose acceptor in good yields. The resulting complex oligosaccharides are useful for vaccine and pharmaceutical applications.


Asunto(s)
Amino Azúcares/química , Amino Azúcares/síntesis química , Oligosacáridos/química , Oligosacáridos/síntesis química , Amino Azúcares/análisis , Catálisis , Técnicas Químicas Combinatorias , Indicadores y Reactivos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Oligosacáridos/análisis , Estereoisomerismo
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