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Serology in the Digital Age: Using Long Synthetic Peptides Created from Nucleic Acid Sequences as Antigens in Microarrays. 数字时代的血清学:利用核酸序列合成的长肽作为微阵列抗原。
Microarrays Pub Date : 2016-08-10 DOI: 10.3390/microarrays5030022
Muhammad Rizwan, Bengt Rönnberg, Maksims Cistjakovs, Åke Lundkvist, Rudiger Pipkorn, Jonas Blomberg
{"title":"Serology in the Digital Age: Using Long Synthetic Peptides Created from Nucleic Acid Sequences as Antigens in Microarrays.","authors":"Muhammad Rizwan,&nbsp;Bengt Rönnberg,&nbsp;Maksims Cistjakovs,&nbsp;Åke Lundkvist,&nbsp;Rudiger Pipkorn,&nbsp;Jonas Blomberg","doi":"10.3390/microarrays5030022","DOIUrl":"https://doi.org/10.3390/microarrays5030022","url":null,"abstract":"<p><strong>Background: </strong>Antibodies to microbes, or to autoantigens, are important markers of disease. Antibody detection (serology) can reveal both past and recent infections. There is a great need for development of rational ways of detecting and quantifying antibodies, both for humans and animals. Traditionally, serology using synthetic antigens covers linear epitopes using up to 30 amino acid peptides.</p><p><strong>Methods: </strong>We here report that peptides of 100 amino acids or longer (\"megapeptides\"), designed and synthesized for optimal serological performance, can successfully be used as detection antigens in a suspension multiplex immunoassay (SMIA). Megapeptides can quickly be created just from pathogen sequences. A combination of rational sequencing and bioinformatic routines for definition of diagnostically-relevant antigens can, thus, rapidly yield efficient serological diagnostic tools for an emerging infectious pathogen.</p><p><strong>Results: </strong>We designed megapeptides using bioinformatics and viral genome sequences. These long peptides were tested as antigens for the presence of antibodies in human serum to the filo-, herpes-, and polyoma virus families in a multiplex microarray system. All of these virus families contain recently discovered or emerging infectious viruses.</p><p><strong>Conclusion: </strong>Long synthetic peptides can be useful as serological diagnostic antigens, serving as biomarkers, in suspension microarrays.</p>","PeriodicalId":56355,"journal":{"name":"Microarrays","volume":"5 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/microarrays5030022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34366360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 12
The Potentials and Pitfalls of Microarrays in Neglected Tropical Diseases: A Focus on Human Filarial Infections. 微阵列在被忽视的热带病中的潜力和缺陷:对人类丝虫病感染的关注。
Microarrays Pub Date : 2016-08-02 DOI: 10.3390/microarrays5030020
Alexander Kwarteng, Samuel Terkper Ahuno
{"title":"The Potentials and Pitfalls of Microarrays in Neglected Tropical Diseases: A Focus on Human Filarial Infections.","authors":"Alexander Kwarteng,&nbsp;Samuel Terkper Ahuno","doi":"10.3390/microarrays5030020","DOIUrl":"https://doi.org/10.3390/microarrays5030020","url":null,"abstract":"<p><p>Data obtained from expression microarrays enables deeper understanding of the molecular signatures of infectious diseases. It provides rapid and accurate information on how infections affect the clustering of gene expression profiles, pathways and networks that are transcriptionally active during various infection states compared to conventional diagnostic methods, which primarily focus on single genes or proteins. Thus, microarray technologies offer advantages in understanding host-parasite interactions associated with filarial infections. More importantly, the use of these technologies can aid diagnostics and helps translate current genomic research into effective treatment and interventions for filarial infections. Studying immune responses via microarray following infection can yield insight into genetic pathways and networks that can have a profound influence on the development of anti-parasitic vaccines. </p>","PeriodicalId":56355,"journal":{"name":"Microarrays","volume":"5 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/microarrays5030020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34366359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Protein Profiling Gastric Cancer and Neighboring Control Tissues Using High-Content Antibody Microarrays. 利用高含量抗体芯片分析胃癌及邻近对照组织的蛋白谱。
Microarrays Pub Date : 2016-07-08 DOI: 10.3390/microarrays5030019
Martin Sill, Christoph Schröder, Ying Shen, Aseel Marzoq, Radovan Komel, Jörg D Hoheisel, Henrik Nienhüser, Thomas Schmidt, Damjana Kastelic
{"title":"Protein Profiling Gastric Cancer and Neighboring Control Tissues Using High-Content Antibody Microarrays.","authors":"Martin Sill,&nbsp;Christoph Schröder,&nbsp;Ying Shen,&nbsp;Aseel Marzoq,&nbsp;Radovan Komel,&nbsp;Jörg D Hoheisel,&nbsp;Henrik Nienhüser,&nbsp;Thomas Schmidt,&nbsp;Damjana Kastelic","doi":"10.3390/microarrays5030019","DOIUrl":"https://doi.org/10.3390/microarrays5030019","url":null,"abstract":"<p><p>In this study, protein profiling was performed on gastric cancer tissue samples in order to identify proteins that could be utilized for an effective diagnosis of this highly heterogeneous disease and as targets for therapeutic approaches. To this end, 16 pairs of postoperative gastric adenocarcinomas and adjacent non-cancerous control tissues were analyzed on microarrays that contain 813 antibodies targeting 724 proteins. Only 17 proteins were found to be differentially regulated, with much fewer molecules than the numbers usually identified in studies comparing tumor to healthy control tissues. Insulin-like growth factor-binding protein 7 (IGFBP7), S100 calcium binding protein A9 (S100A9), interleukin-10 (IL-10) and mucin 6 (MUC6) exhibited the most profound variations. For an evaluation of the proteins' capacity for discriminating gastric cancer, a Receiver Operating Characteristic curve analysis was performed, yielding an accuracy (area under the curve) value of 89.2% for distinguishing tumor from non-tumorous tissue. For confirmation, immunohistological analyses were done on tissue slices prepared from another cohort of patients with gastric cancer. The utility of the 17 marker proteins, and particularly the four molecules with the highest specificity for gastric adenocarcinoma, is discussed for them to act as candidates for diagnosis, even in serum, and targets for therapeutic approaches. </p>","PeriodicalId":56355,"journal":{"name":"Microarrays","volume":"5 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/microarrays5030019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34366358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
MicroRNA Profile of Lung Tumor Tissues Is Associated with a High Risk Plasma miRNA Signature. 肺肿瘤组织MicroRNA谱与高危血浆miRNA信号相关
Microarrays Pub Date : 2016-07-05 DOI: 10.3390/microarrays5030018
Orazio Fortunato, Carla Verri, Ugo Pastorino, Gabriella Sozzi, Mattia Boeri
{"title":"MicroRNA Profile of Lung Tumor Tissues Is Associated with a High Risk Plasma miRNA Signature.","authors":"Orazio Fortunato,&nbsp;Carla Verri,&nbsp;Ugo Pastorino,&nbsp;Gabriella Sozzi,&nbsp;Mattia Boeri","doi":"10.3390/microarrays5030018","DOIUrl":"https://doi.org/10.3390/microarrays5030018","url":null,"abstract":"<p><p>Lung cancer is the most common cause of cancer deaths worldwide. MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression. Many studies have reported that alterations in miRNA expression are involved in several human tumors. We have previously identified a circulating miRNA signature classifier (MSC) able to discriminate lung cancer with more aggressive features. In the present work, microarray miRNA profiling of tumor tissues collected from 19 lung cancer patients with an available MSC result were perform in order to find a possible association between miRNA expression and the MSC risk level. Eleven tissue mature miRNAs and six miRNA precursors were observed to be associated with the plasma MSC risk level of patients. Not one of these miRNAs was included in the MSC algorithm. A pathway enrichment analysis revealed a role of these miRNA in the main pathways determining lung cancer aggressiveness. Overall, these findings add to the knowledge that tissue and plasma miRNAs behave as excellent diagnostic and prognostic biomarkers, which may find rapid application in clinical settings. </p>","PeriodicalId":56355,"journal":{"name":"Microarrays","volume":"5 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/microarrays5030018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34366388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 10
SNPConvert: SNP Array Standardization and Integration in Livestock Species. SNPConvert:家畜SNP阵列标准化与整合。
Microarrays Pub Date : 2016-06-09 DOI: 10.3390/microarrays5020017
Ezequiel Luis Nicolazzi, Gabriele Marras, Alessandra Stella
{"title":"SNPConvert: SNP Array Standardization and Integration in Livestock Species.","authors":"Ezequiel Luis Nicolazzi,&nbsp;Gabriele Marras,&nbsp;Alessandra Stella","doi":"10.3390/microarrays5020017","DOIUrl":"https://doi.org/10.3390/microarrays5020017","url":null,"abstract":"<p><p>One of the main advantages of single nucleotide polymorphism (SNP) array technology is providing genotype calls for a specific number of SNP markers at a relatively low cost. Since its first application in animal genetics, the number of available SNP arrays for each species has been constantly increasing. However, conversely to that observed in whole genome sequence data analysis, SNP array data does not have a common set of file formats or coding conventions for allele calling. Therefore, the standardization and integration of SNP array data from multiple sources have become an obstacle, especially for users with basic or no programming skills. Here, we describe the difficulties related to handling SNP array data, focusing on file formats, SNP allele coding, and mapping. We also present SNPConvert suite, a multi-platform, open-source, and user-friendly set of tools to overcome these issues. This tool, which can be integrated with open-source and open-access tools already available, is a first step towards an integrated system to standardize and integrate any type of raw SNP array data. The tool is available at: https://github. com/nicolazzie/SNPConvert.git. </p>","PeriodicalId":56355,"journal":{"name":"Microarrays","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/microarrays5020017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34366387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
Evaluation of Solid Supports for Slide- and Well-Based Recombinant Antibody Microarrays. 载玻片和孔基重组抗体微阵列固体载体的评价。
Microarrays Pub Date : 2016-06-08 DOI: 10.3390/microarrays5020016
Anna S Gerdtsson, Linda Dexlin-Mellby, Payam Delfani, Erica Berglund, Carl A K Borrebaeck, Christer Wingren
{"title":"Evaluation of Solid Supports for Slide- and Well-Based Recombinant Antibody Microarrays.","authors":"Anna S Gerdtsson,&nbsp;Linda Dexlin-Mellby,&nbsp;Payam Delfani,&nbsp;Erica Berglund,&nbsp;Carl A K Borrebaeck,&nbsp;Christer Wingren","doi":"10.3390/microarrays5020016","DOIUrl":"https://doi.org/10.3390/microarrays5020016","url":null,"abstract":"<p><p>Antibody microarrays have emerged as an important tool within proteomics, enabling multiplexed protein expression profiling in both health and disease. The design and performance of antibody microarrays and how they are processed are dependent on several factors, of which the interplay between the antibodies and the solid surfaces plays a central role. In this study, we have taken on the first comprehensive view and evaluated the overall impact of solid surfaces on the recombinant antibody microarray design. The results clearly demonstrated the importance of the surface-antibody interaction and showed the effect of the solid supports on the printing process, the array format of planar arrays (slide- and well-based), the assay performance (spot features, reproducibility, specificity and sensitivity) and assay processing (degree of automation). In the end, two high-end recombinant antibody microarray technology platforms were designed, based on slide-based (black polymer) and well-based (clear polymer) arrays, paving the way for future large-scale protein expression profiling efforts. </p>","PeriodicalId":56355,"journal":{"name":"Microarrays","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/microarrays5020016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34366386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 12
Enhancing Interpretability of Gene Signatures with Prior Biological Knowledge. 利用先验生物学知识增强基因特征的可解释性。
Microarrays Pub Date : 2016-06-08 DOI: 10.3390/microarrays5020015
Margherita Squillario, Matteo Barbieri, Alessandro Verri, Annalisa Barla
{"title":"Enhancing Interpretability of Gene Signatures with Prior Biological Knowledge.","authors":"Margherita Squillario,&nbsp;Matteo Barbieri,&nbsp;Alessandro Verri,&nbsp;Annalisa Barla","doi":"10.3390/microarrays5020015","DOIUrl":"https://doi.org/10.3390/microarrays5020015","url":null,"abstract":"<p><p>Biological interpretability is a key requirement for the output of microarray data analysis pipelines. The most used pipeline first identifies a gene signature from the acquired measurements and then uses gene enrichment analysis as a tool for functionally characterizing the obtained results. Recently Knowledge Driven Variable Selection (KDVS), an alternative approach which performs both steps at the same time, has been proposed. In this paper, we assess the effectiveness of KDVS against standard approaches on a Parkinson's Disease (PD) dataset. The presented quantitative analysis is made possible by the construction of a reference list of genes and gene groups associated to PD. Our work shows that KDVS is much more effective than the standard approach in enhancing the interpretability of the obtained results. </p>","PeriodicalId":56355,"journal":{"name":"Microarrays","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/microarrays5020015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34366385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Retrospective Proteomic Analysis of Cellular Immune Responses and Protective Correlates of p24 Vaccination in an HIV Elite Controller Using Antibody Arrays. 使用抗体阵列对HIV精英控制者中p24疫苗接种的细胞免疫应答和保护性相关因素进行回顾性蛋白质组学分析。
Microarrays Pub Date : 2016-06-02 DOI: 10.3390/microarrays5020014
Suneth S Perera, Bin Wang, Arturo Damian, Wayne Dyer, Li Zhou, Viviane Conceicao, Nitin K Saksena
{"title":"Retrospective Proteomic Analysis of Cellular Immune Responses and Protective Correlates of p24 Vaccination in an HIV Elite Controller Using Antibody Arrays.","authors":"Suneth S Perera,&nbsp;Bin Wang,&nbsp;Arturo Damian,&nbsp;Wayne Dyer,&nbsp;Li Zhou,&nbsp;Viviane Conceicao,&nbsp;Nitin K Saksena","doi":"10.3390/microarrays5020014","DOIUrl":"https://doi.org/10.3390/microarrays5020014","url":null,"abstract":"<p><strong>Background: </strong>HIV p24 is an extracellular HIV antigen involved in viral replication. Falling p24 antibody responses are associated with clinical disease progression and their preservation with non-progressive disease. Stimulation of p24 antibody production by immunization to delay progression was the basis of discontinued p24 vaccine. We studied a therapy-naive HIV+ man from Sydney, Australia, infected in 1988. He received the HIV-p24-virus like particle (VLP) vaccine in 1993, and continues to show vigorous p24 antigen responses (>4% p24-specific CD4⁺ T cells), coupled with undetectable plasma viremia. We defined immune-protective correlates of p24 vaccination at the proteomic level through parallel retrospective analysis of cellular immune responses to p24 antigen in CD4⁺ and CD8⁺ T cells and CD14⁺ monocytes at viremic and aviremic phases using antibody-array. We found statistically significant coordinated up-regulation by all three cell-types with high fold-changes in fractalkine, ITAC, IGFBP-2, and MIP-1α in the aviremic phase. TECK and TRAIL-R4 were down-regulated in the viremic phase and up-regulated in the aviremic phase. The up-regulation of fractalkine in all three cell-types coincided with protective effect, whereas the dysfunction in anti-apoptotic chemokines with the loss of immune function. This study highlights the fact that induction of HIV-1-specific helper cells together with coordinated cellular immune response (p < 0.001) might be important in immunotherapeutic interventions and HIV vaccine development.</p>","PeriodicalId":56355,"journal":{"name":"Microarrays","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/microarrays5020014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34366384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 5
Advantages of Array-Based Technologies for Pre-Emptive Pharmacogenomics Testing. 预先药物基因组学检测的阵列技术优势
Microarrays Pub Date : 2016-05-28 DOI: 10.3390/microarrays5020012
Al Shahandeh, Daniel M Johnstone, Joshua R Atkins, Jean-Marie Sontag, Moones Heidari, Nilofar Daneshi, Elvis Freeman-Acquah, Elizabeth A Milward
{"title":"Advantages of Array-Based Technologies for Pre-Emptive Pharmacogenomics Testing.","authors":"Al Shahandeh,&nbsp;Daniel M Johnstone,&nbsp;Joshua R Atkins,&nbsp;Jean-Marie Sontag,&nbsp;Moones Heidari,&nbsp;Nilofar Daneshi,&nbsp;Elvis Freeman-Acquah,&nbsp;Elizabeth A Milward","doi":"10.3390/microarrays5020012","DOIUrl":"https://doi.org/10.3390/microarrays5020012","url":null,"abstract":"<p><p>As recognised by the National Institutes of Health (NIH) Precision Medicine Initiative (PMI), microarray technology currently provides a rapid, inexpensive means of identifying large numbers of known genomic variants or gene transcripts in experimental and clinical settings. However new generation sequencing techniques are now being introduced in many clinical genetic contexts, particularly where novel mutations are involved. While these methods can be valuable for screening a restricted set of genes for known or novel mutations, implementation of whole genome sequencing in clinical practice continues to present challenges. Even very accurate high-throughput methods with small error rates can generate large numbers of false negative or false positive errors due to the high numbers of simultaneous readings. Additional validation is likely to be required for safe use of any such methods in clinical settings. Custom-designed arrays can offer advantages for screening for common, known mutations and, in this context, may currently be better suited for accredited, quality-controlled clinical genetic screening services, as illustrated by their successful application in several large-scale pre-emptive pharmacogenomics programs now underway. Excessive, inappropriate use of next-generation sequencing may waste scarce research funds and other resources. Microarrays presently remain the technology of choice in applications that require fast, cost-effective genome-wide screening of variants of known importance, particularly for large sample sizes. This commentary considers some of the applications where microarrays continue to offer advantages over next-generation sequencing technologies. </p>","PeriodicalId":56355,"journal":{"name":"Microarrays","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/microarrays5020012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34366383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
Small-Molecule Inhibition of Rho/MKL/SRF Transcription in Prostate Cancer Cells: Modulation of Cell Cycle, ER Stress, and Metastasis Gene Networks. 前列腺癌细胞中Rho/MKL/SRF转录的小分子抑制:细胞周期、内质网应激和转移基因网络的调节
Microarrays Pub Date : 2016-05-28 DOI: 10.3390/microarrays5020013
Chris R Evelyn, Erika M Lisabeth, Susan M Wade, Andrew J Haak, Craig N Johnson, Elizabeth R Lawlor, Richard R Neubig
{"title":"Small-Molecule Inhibition of Rho/MKL/SRF Transcription in Prostate Cancer Cells: Modulation of Cell Cycle, ER Stress, and Metastasis Gene Networks.","authors":"Chris R Evelyn,&nbsp;Erika M Lisabeth,&nbsp;Susan M Wade,&nbsp;Andrew J Haak,&nbsp;Craig N Johnson,&nbsp;Elizabeth R Lawlor,&nbsp;Richard R Neubig","doi":"10.3390/microarrays5020013","DOIUrl":"https://doi.org/10.3390/microarrays5020013","url":null,"abstract":"<p><p>Metastasis is the major cause of cancer deaths and control of gene transcription has emerged as a critical contributing factor. RhoA- and RhoC-induced gene transcription via the actin-regulated transcriptional co-activator megakaryocytic leukemia (MKL) and serum response factor (SRF) drive metastasis in breast cancer and melanoma. We recently identified a compound, CCG-1423, which blocks Rho/MKL/SRF-mediated transcription and inhibits PC-3 prostate cancer cell invasion. Here, we undertook a genome-wide expression study in PC-3 cells to explore the mechanism and function of this compound. There was significant overlap in the genes modulated by CCG-1423 and Latrunculin B (Lat B), which blocks the Rho/MKL/SRF pathway by preventing actin polymerization. In contrast, the general transcription inhibitor 5,6-dichloro-1-β-d-ribofuranosyl-1H-benzimidazole (DRB) showed a markedly different pattern. Effects of CCG-1423 and Lat B on gene expression correlated with literature studies of MKL knock-down. Gene sets involved in DNA synthesis and repair, G1/S transition, and apoptosis were modulated by CCG-1423. It also upregulated genes involved in endoplasmic reticulum stress. Targets of the known Rho target transcription factor family E2F and genes related to melanoma progression and metastasis were strongly suppressed by CCG-1423. These results confirm the ability of our compound to inhibit expression of numerous Rho/MKL-dependent genes and show effects on stress pathways as well. This suggests a novel approach to targeting aggressive cancers and metastasis. </p>","PeriodicalId":56355,"journal":{"name":"Microarrays","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/microarrays5020013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34365919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 21
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