检索结果-内蒙古大学图书馆

Epigenetic targeting of the Nanog pathway and signaling networks during chemical carcinogenesis

CARCINOGENESIS 2014年第8期35卷 1726-1736页

作者： Tommasi, Stella Zheng, Albert Yoon, Jae-In Besaratinia, Ahmad Univ So Calif Keck Sch Med Dept Prevent Med Los Angeles CA 90033 USA QIAGEN Seoul South Korea

Chemical carcinogenesis has long been synonymous with genotoxicity, which entails DNA damage, genetic mutations and chromosomal abnormalities. The present study investigates a paradigm-shifting model in which epigenetic changes are key contributors to chemical carcinogenesis. Using genome-wide microarray-based analysis followed by conventional validation assays, we have progressively chronicled changes in the epigenetic landscape, as reflected in the patterns of DNA methylation, in the target organ of tumorigenesis in mice treated in vivo with a prototype chemical carcinogen (benzo[a] pyrene). Here, we demonstrate characteristic CpG island gain/loss of methylation and demethylation of repetitive DNA elements in carcinogen-treated mice, dependent on tumor progression. Alterations of the DNA methylome are accompanied by silencing of major DNA methyltransferases. Members of the Nanog pathway that establishes and maintains pluripotency in embryonic stem cells and possibly triggers uncontrolled proliferation of neoplastic cells are preferential targets of aberrant DNA methylation and concomitant gene dysregulation during chemical carcinogenesis. Several components of the MEK/ERK, JAK/STAT3, PI3K/AKT, WNT/beta-catenin and Shh signaling cascades, which are known to modulate Nanog expression, also show concurrent changes in the patterns of DNA methylation and gene expression. Our data support an epigenetic model of chemical carcinogenesis and suggest that surveillance of the epigenetic landscape, particularly at the loci and in the pathways identified in this study, may have utility for early detection and monitoring of the progression of malignancy.

关键词： EPIGENETICS GENE targeting CARCINOGENESIS STAT proteins GENOMES microarray technology DNA damage DNA methylation

来源：评论

学校读者我要写书评

暂无评论

Latex-less opium poppy: cause for less latex and reduced peduncle strength

引用

PHYSIOLOGIA PLANTARUM 2014年第3期150卷 436-445页

作者： Chaturvedi, Nidarshana Singh, Sharad K. Shukla, Ashutosh K. Lal, Raj K. Gupta, Madan M. Dwivedi, Upendra N. Shasany, Ajit K. CSIR Cent Inst Med & Aromat Plants Div Biotechnol Lucknow 226015 Uttar Pradesh India CSIR Cent Inst Med & Aromat Plants Lucknow 226015 Uttar Pradesh India CSIR Cent Inst Med & Aromat Plants Div Analyt Chem Lucknow 226015 Uttar Pradesh India Univ Lucknow Dept Biochem Lucknow 226007 Uttar Pradesh India

A genotype Sujata' developed earlier at CSIR-CIMAP from its parent Sampada' is considered to be the latex-less variety of Papaver somniferum. These two genotypes are contrasting in terms of latex and stem strength. Earlier we have carried out microarray analysis to identify differentially expressing genes from the capsules of the two genotypes. In this study, the peduncles of the two genotypes were compared for the anatomy revealing less number of laticifers in the cortex and vascular bundles. One of the important cell wall-related genes (for laccase) from the microarray analysis showing significantly higher expression in Sampada' capsule was taken up for further characterization in the peduncle here. It was functionally characterized through transient overexpression and RNAi suppression in Sujata' and Sampada'. The increase in acid insoluble lignin and total lignin in overexpressed tissue of Sujata', and comparable decrease in suppressed tissue of Sampada', along with corresponding increase and decrease in the transcript abundance of laccase confirm the involvement of laccase in lignin biosynthesis. Negligible transcript in phloem compared to the xylem tissue localized its expression in xylem tissue. This demonstrates the involvement of P. somniferum laccase in lignin biosynthesis of xylem, providing strength to the peduncle/stem and preventing lodging.

关键词： OPIUM poppy LATEX microarray technology GENE expression CORTEX (Botany) BIOSYNTHESIS

来源：评论

学校读者我要写书评

暂无评论

EGCG Enhances the Efficacy of Cisplatin by Downregulating hsa-miR-98-5p in NSCLC A549 Cells

引用

NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL 2014年第4期66卷 636-644页

作者： Zhou, Dong-Hu Wang, Xuemin Feng, Qing Nanjing Med Univ Sch Publ Hlth Key Lab Toxicol Dept Nutr & Food Safety Nanjing 211166 Jiangsu Peoples R China

In the current study, the enhanced efficacy of cisplatin caused by (-)-epigallocatechin-3-gallate (EGCG) in nonsmall cell lung cancer (NSCLC) A549 cells was observed. The tumor size was significantly smaller in vivo in the combination of cisplatin and EGCG group, as compared with cisplatin-only group. However, in NCI-H460 cells, another kind of NSCLC cells, the efficacy of cisplatin was antagonized by EGCG. MiRNA microarray showed that hsa-miR-98-5p and hsa-miR-125a-3p were differentially expressed after EGCG treatment in these 2 cell lines. After transfection of hsa-miR-98-5p inhibitor, the survival fraction of both A549 and NCI-H460 cells was decreased upon cisplatin treatment. Meanwhile, as a critical regulator in the cisplatin-induced apoptosis, p53 was elevated by silencing of hsa-miR-98-5p. These results suggested that EGCG inhibited the expression of hsa-miR-98-5p, followed by an increase of p53, thus the efficacy of cisplatin was enhanced. Bioinformatics analysis showed that hsa-miR-125a-3p might have a strong connection with classical MAPK pathway. Taken together, these findings indicate that hsa-miR-98-5p could be a potential target in clinical cisplatin treatment of NSCLC. The combination of EGCG and cisplatin might be an effective therapeutic strategy in treating some type of NSCLC, although the possibility of antagonistic interactions must also be taken into account.

关键词： CISPLATIN RNA -- Physiology ACIDS BIOPHYSICS CANCER patients LUNGS -- Cancer LUNG tumors RESEARCH -- Methodology NUTRITION POLYMERASE chain reaction DATA analysis microarray technology DESCRIPTIVE statistics THERAPEUTIC use

来源：评论

学校读者我要写书评

暂无评论

Relationship of Gene Expression in the Injured Human Meniscus to Body Mass Index A Biologic Connection Between Obesity and Osteoarthritis

引用

ARTHRITIS & RHEUMATOLOGY 2014年第8期66卷 2152-2164页

作者： Rai, Muhammad Farooq Patra, Debabrata Sandell, Linda J. Brophy, Robert H. Washington Univ Sch Med Barnes Jewish Hosp St Louis MO USA

Objective. Higher body mass index (BMI) increases the risk of meniscus injury and knee osteoarthritis (OA). However, it is unknown if and how obesity affects meniscus biology. We analyzed transcriptome-wide gene expression profiles of injured human menisci to test the hypothesis that meniscal gene expression signatures relate to patient BMI. Methods. Meniscus samples were obtained from patients undergoing arthroscopic partial meniscectomy. Transcriptome- wide analysis of gene expression followed by validation of selected transcripts by Quanti-Gene Plex assay was performed. Correlations of gene expression with BMI and relative fold changes (>= 1.5-fold) in 3 BMI categories (lean [BMI 18.5-24.9 kg/m(2)], overweight [BMI 25.0- 29.9 kg/m(2)], and obese [BMI >30.0 kg/m(2)]) were analyzed, and integrated functional classifications were probed computationally. Results. The obese versus overweight comparison resulted in the largest set of differences (565 transcripts) followed by obese versus lean (280 transcripts) and overweight versus lean (125 transcripts). Biologic reproducibility was confirmed by cluster analysis of expressed transcripts. Differentially regulated transcripts represented important functional classifications. Transcripts associated with oxygen transport, calcium ion binding, and cell homeostasis were elevated with BMI, while those related to extracellular matrix deposition, cell migration, and glucosamine metabolic processes were repressed. While these functional classifications may play key roles in cartilage/meniscus homeostasis, failure of extracellular matrix deposition and increase in calcium ion binding likely contribute to OA development following meniscal injury. Conclusion. Our results indicate greater differences in gene expression between obese and overweight groups than between overweight and lean groups. This may indicate that there is a weight threshold at which injured meniscus responds severely to increased BMI. BMI-related changes in gen

关键词： OSTEOARTHRITIS OBESITY complications MENISCUS injuries ACADEMIC medical centers ANALYSIS of variance CORRELATION (Statistics) FISHER exact test FINANCING of research STATISTICS GENOMICS DATA analysis BODY mass index microarray technology DESCRIPTIVE statistics RISK factors GENETIC aspects

来源：评论

学校读者我要写书评

暂无评论

Genome-Wide DNA Methylation Study Identifies Significant Epigenomic Changes in Osteoarthritic Cartilage

引用

ARTHRITIS & RHEUMATOLOGY 2014年第10期66卷 2804-2815页

作者： Jeffries, Matlock A. Donica, Madison Baker, Lyle W. Stevenson, Michael E. Annan, Anand C. Humphrey, Mary Beth James, Judith A. Sawalha, Amr H. Univ Oklahoma Hlth Sci Ctr Oklahoma City OK USA Oklahoma Med Res Fdn Oklahoma City OK 73104 USA Oklahoma Med Res Fdn Oklahoma City OK 73104 USA Univ Oklahoma Oklahoma City OK USA Univ Oklahoma Hlth Sci Ctr Oklahoma City OK USA Univ Oklahoma Hlth Sci Ctr Oklahoma Med Res Fdn Oklahoma City OK USA Dept Vet Affairs Med Ctr Oklahoma City OK USA Univ Michigan Ann Arbor MI 48109 USA

ObjectiveTo perform a genome-wide DNA methylation study to identify DNA methylation changes in osteoarthritic (OA) cartilage tissue. MethodsThe contribution of differentially methylated genes to OA pathogenesis was assessed by bioinformatic analysis, gene expression analysis, and histopathologic severity correlation. Genome-wide DNA methylation profiling of >485,000 methylation sites was performed on eroded and intact cartilage from within the same joint of 24 patients undergoing hip arthroplasty for OA. Genes with differentially methylated CpG sites were analyzed to identify overrepresented gene ontologies, pathways, and upstream regulators. The messenger RNA expression of a subset of differentially methylated genes was analyzed by reverse transcription-polymerase chain reaction. Histopathology was graded by modified Mankin score and correlated with DNA methylation. ResultsWe identified 550 differentially methylated sites in OA. Most (69%) were hypomethylated and enriched among gene enhancers. We found differential methylation in genes with prior links to OA, including RUNX1, RUNX2, DLX5, FURIN, HTRA1, FGFR2, NFATC1, SNCAIP, and COL11A2. Among these, RUNX1, HTRA1, FGFR2, and COL11A2 were also differentially expressed. Furthermore, we found differential methylation in approximately one-third of known OA susceptibility genes. Among differentially methylated genes, upstream regulator analysis showed enrichment of TGFB1 (P = 4.40 x 10(-5)) and several microRNAs including miR-128 (P = 4.48 x 10(-13)), miR-27a (P = 4.15 x 10(-12)), and miR-9 (P = 9.20 x 10(-10)). Finally, we identified strong correlations between 20 CpG sites and the histologic Mankin score in OA. ConclusionOur data implicate epigenetic dysregulation of a host of genes and pathways in OA, including a number of OA susceptibility genes. Furthermore, we identified correlations between CpG methylation and histologic severity in OA.

关键词： OSTEOARTHRITIS CARTILAGE physiology ACADEMIC medical centers CHI-squared test GENE expression GENETIC polymorphisms METHYLATION MUTATION (Biology) POLYMERASE chain reaction REGRESSION analysis FINANCING of research STATISTICS GENOMICS DATA analysis DISEASE incidence SEVERITY of illness index REVERSE transcriptase polymerase chain reaction microarray technology GENETIC aspects

来源：评论

学校读者我要写书评

暂无评论

Identification of Stage-Specific Genes Associated With Lupus Nephritis and Response to Remission Induction in (NZB x NZW)F1 and NZM2410 Mice

引用

ARTHRITIS & RHEUMATOLOGY 2014年第8期66卷 2246-2258页

作者： Bethunaickan, Ramalingam Berthier, Celine C. Zhang, Weijia Eksi, Ridvan Li, Hong-Dong Guan, Yuanfang Kretzler, Matthias Davidson, Anne Feinstein Inst Med Res Manhasset NY USA Univ Michigan Ann Arbor MI 48109 USA Mt Sinai Med Ctr New York NY 10029 USA

Objective. To elucidate the molecular mechanisms involved in renal inflammation during the progression, remission, and relapse of nephritis in murine lupus models using transcriptome analysis. Methods. Kidneys from (NZB x NZW)F1 (NZB/NZW) and NZM2410 mice were harvested at intervals during the disease course or after remission induction. Genome-wide expression profiles were obtained from microarray analysis of perfused kidneys. Real-time polymerase chain reaction (PCR) analysis for selected genes was used to validate the microarray data. Comparisons between groups using SAM, and unbiased analysis of the entire data set using singular value decomposition and self-organizing maps were performed. Results. Few changes in the renal molecular profile were detected in prenephritic kidneys, but a significant shift in gene expression, reflecting inflammatory cell infiltration and complement activation, occurred at proteinuria onset. Subsequent changes in gene expression predominantly affected mitochondrial dysfunction and metabolic stress pathways. Endothelial cell activation, tissue remodeling, and tubular damage were the major pathways associated with loss of renal function. Remission induction reversed most, but not all, of the inflammatory changes, and progression toward relapse was associated with recurrence of inflammation, mitochondrial dysfunction, and metabolic stress signatures. Conclusion. Immune cell infiltration and activation is associated with proteinuria onset and is reversed by immunosuppressive therapy, but disease progression is associated with renal hypoxia and metabolic stress. Optimal therapy for lupus nephritis may therefore need to target both immune and nonimmune disease mechanisms. In addition, the overlap of a substantial subset of molecular markers with those expressed in the kidneys of lupus patients suggests potential new biomarkers and therapeutic targets.

关键词： LUPUS nephritis ACADEMIC medical centers ANIMAL experimentation MICE POLYMERASE chain reaction FINANCING of research U-statistics microarray technology GENETIC aspects

来源：评论

学校读者我要写书评

暂无评论

Modular Transcriptional Repertoire Analyses of Adults With Systemic Lupus Erythematosus Reveal Distinct Type I and Type II Interferon Signatures

引用

ARTHRITIS & RHEUMATOLOGY 2014年第6期66卷 1583-1595页

作者： Chiche, Laurent Jourde-Chiche, Noemie Whalen, Elizabeth Presnell, Scott Gersuk, Vivian Dang, Kristen Anguiano, Esperanza Quinn, Charlie Burtey, Stephane Berland, Yvon Kaplanski, Gilles Harle, Jean-Robert Pascual, Virginia Chaussabel, Damien Benaroya Res Inst Seattle WA USA Aix Marseille Univ Marseille France Hop Conception APHM F-13005 Marseille France Baylor Inst Immunol Res Dallas TX USA

Objective. The role of interferon-alpha (IFN alpha) in the pathogenesis of systemic lupus erythematosus (SLE) is strongly supported by gene expression studies. The aim of this study was to improve characterization of the blood IFN signature in adult SLE patients. Methods. Consecutive patients were enrolled and followed up prospectively. microarray data were generated using Illumina BeadChips. A modular transcriptional repertoire was used as a framework for the analysis. Results. Our repertoire of 260 modules, which consisted of coclustered gene sets, included 3 IFN-annotated modules (M1.2, M3.4, and M5.12) that were strongly up-regulated in SLE patients. A modular IFN signature was observed in 54 of 62 patients (87%) or 131 of all 157 samples (83%). The IFN signature was more complex than expected, with each module displaying a distinct activation threshold (M1.2 < M3.4 < M5.12), thus providing a modular score by which to stratify SLE patients based on the presence of 0, 1, 2, or 3 active IFN modules. A similar gradient in modular IFN signature was observed within patients with clinically quiescent disease, for whom moderate/strong modular scores (2 or 3 active IFN modules) were associated with higher anti-double-stranded DNA titers and lower lymphocyte counts than those in patients with absent/mild modular scores (0 or 1 active IFN modules). Longitudinal analyses revealed both stable (M1.2) and variable (M3.4 and M5.12) components of modular IFN signature over time in single patients. Interestingly, mining of other data sets suggested that M3.4 and M5.12 could also be driven by IFN beta and IFN gamma. Conclusion. Modular repertoire analysis reveals complex IFN signatures in SLE, which are not restricted to the previous IFN alpha signature, but which also involve IFN beta and IFN gamma

关键词： ACADEMIC medical centers AUTOANTIBODIES CHI-squared test CLINICAL trials CORRELATION (Statistics) FISHER exact test INTERFERONS LONGITUDINAL method PUBLIC health surveillance FINANCING of research STATISTICS SYSTEMIC lupus erythematosus T-test (Statistics) PHENOTYPE DATA analysis SEVERITY of illness index DISEASE duration DATA analysis software microarray technology GENE expression profiling DESCRIPTIVE statistics

来源：评论

学校读者我要写书评

暂无评论

Molecular phenotypic profiling of a Saccharomyces cerevisiae strain at the single-cell level

引用

ANALYST 2014年第22期139卷 5709-5717页

作者： Schmidt, A. Mareike Fagerer, Stephan R. Jefimovs, Konstantins Buettner, Florian Marro, Christian Siringil, Erdem C. Boehlen, Karl L. Pabst, Martin Ibanez, Alfredo J. ETH Inst Mol Syst Biol CH-8093 Zurich Switzerland ETH Dept Chem & Appl Biosci CH-8093 Zurich Switzerland Swiss Fed Inst Mat Sci & Technol EMPA Lab Elect Metrol Reliabil CH-8600 Dubendorf Switzerland Helmholtz Zentrum Munchen Inst Computat Biol D-85764 Neuherberg Germany Swiss Fed Inst Mat Sci & Technol EMPA Lab Adv Mat Proc CH-3602 Thun Switzerland

Studying cell-to-cell heterogeneity requires techniques which robustly deliver reproducible results with single-cell sensitivity. Through a new fabrication method for the microarrays for mass spectrometry (MAMS) platform, we now have attained robustness and reproducibility in our single-cell level mass spectrometry measurements that allowed us to combine single-cell MAMS-based measurements from different days and samples. By combining multiple measurements, we were able to identify three coexisting phenotypes in an isogenic population of Saccharomyces cerevisiae characterized by distinctively different levels of glycolytic intermediates.

关键词： CELL interaction (Biology) RESEARCH SACCHAROMYCES cerevisiae GLYCOLYSIS microarray technology MASS spectrometry MOLECULAR probes

来源：评论

学校读者我要写书评

暂无评论

Combining optimization and machine learning techniques for genome-wide prediction of human cell cycle-regulated genes

引用

BIOINFORMATICS 2014年第2期30卷 228-233页

作者： De Santis, Marianna Rinaldi, Francesco Falcone, Emmanuela Lucidi, Stefano Piaggio, Giulia Gurtner, Aymone Farina, Lorenzo Sapienza Univ Roma Dipartimento Ingn Informat Automat & Gestionale Rome Italy Ist Nazl Tumori Regina Elena Dipartimento Oncol Sperimentale Lab Oncogenesi Mol Rome Italy

Motivation: The identification of cell cycle-regulated genes through the cyclicity of messenger RNAs in genome-wide studies is a difficult task due to the presence of internal and external noise in microarray data. Moreover, the analysis is also complicated by the loss of synchrony occurring in cell cycle experiments, which often results in additional background noise. Results: To overcome these problems, here we propose the LEON (LEarning and OptimizatioN) algorithm, able to characterize the 'cyclicity degree' of a gene expression time profile using a two-step cascade procedure. The first step identifies a potentially cyclic behavior by means of a Support Vector Machine trained with a reliable set of positive and negative examples. The second step selects those genes having peak timing consistency along two cell cycles by means of a non-linear optimization technique using radial basis functions. To prove the effectiveness of our combined approach, we use recently published human fibroblasts cell cycle data and, performing in vivo experiments, we demonstrate that our computational strategy is able not only to confirm well-known cell cycle-regulated genes, but also to predict not yet identified ones.

关键词： MACHINE learning CELL cycle -- Regulation MESSENGER RNA microarray technology SUPPORT vector machines MATHEMATICAL optimization

来源：评论

学校读者我要写书评

暂无评论

MUC5AC expression correlates with invasiveness and progression of extramammary Paget's disease

引用

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY 2014年第6期28卷 727-732页

作者： Hata, H. Abe, R. Hoshina, D. Saito, N. Homma, E. Aoyagi, S. Shimizu, H. Hokkaido Univ Grad Sch Med Dept Dermatol Sapporo Hokkaido Japan

BackgroundPatients with in situ extramammary Paget's disease (EMPD) tend to have a good prognosis, although dermal invasion and metastasis are associated with significantly increased morbidity and mortality. Previous studies have addressed mechanisms underlying the EMPD pathogenesis;however, no molecular markers that reflect invasiveness or progression have been established. ObjectiveThis study aims to identify a reliable marker for predicting the risk of invasion and metastasis in EMPD. MethodsWe performed an initial microarray screening for in situ, invasive or metastatic lymph node lesions of EMPD. We analysed 44 specimens from 38 primary EMPD cases by immunohistochemical staining. ResultsWe found that expressions of MUC5AC directly correlate with invasion and prognosis. Labelling rates of tumour cells were scored by staining intensity on a four-tiered scale (- to 3+) to investigate the correlation between the expression score of these molecular markers and the type of EMPD lesion. All the specimens scored positive (3+) for MUC1 and negative (-) for MUC6. MUC5AC expression was detected in 19 of 44 (43.2%) specimens. Invasive lesions and metastatic lymph nodes tended to express MUC5AC significantly higher than in situ lesions (P<0.01). MUC2 was positive in 10 specimens (22.7%). There was no significant difference between the degree of MUC2 expression and invasiveness. ConclusionThe degree of MUC5AC expression may correlate with the invasiveness and progression of EMPD, and may be a useful marker for identifying high-risk EMPD cases.

关键词： OSTEITIS deformans RESEARCH GENE expression BONE metastasis LYMPH nodes -- Diseases PRECANCEROUS conditions microarray technology GENETIC aspects

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：