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https://www.readbyqxmd.com/read/29146205/pax3-foxo1-zooming-in-on-an-undruggable-target
#1
REVIEW
Marco Wachtel, Beat W Schäfer
Driver oncogenes are prime targets for therapy in tumors many of which, including leukemias and sarcomas, express recurrent fusion transcription factors. One specific example for such a cancer type is alveolar rhabdomyosarcoma, which is associated in the majority of cases with the fusion protein PAX3-FOXO1. Since fusion transcription factors are challenging targets for development of small molecule inhibitors, indirect inhibitory strategies for this type of oncogenes represent a more promising approach. One can envision strategies at different molecular levels including upstream modifiers and activators, epigenetic and transcriptional co-regulators, and downstream effector targets...
November 13, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29145706/expression-of-oestrogen-receptors-gper-esr1-esr2-in-human-ductuli-efferentes-and-proximal-epididymis
#2
V Rago, F Romeo, F Giordano, R Malivindi, V Pezzi, I Casaburi, A Carpino
Oestrogen targeting in the human genital ducts is still not well-known. In fact, to date, the localization of oestrogen receptors, ESR1 and ESR2, is controversial and the presence of the membrane oestrogen receptor GPER (G protein-coupled oestrogen receptor) is unexplored. This study has investigated the expression of GPER, ESR1, ESR2 in human ductuli efferentes and proximal caput epididymis by immunohistochemistry and Western blot analysis. Furthermore, the presence of PELP1 (proline-glutamic acid-leucine-rich protein 1), a co-regulator of the oestrogen receptors, was also evaluated...
November 16, 2017: Andrology
https://www.readbyqxmd.com/read/29144947/re-the-metabolic-co-regulator-pgc1%C3%AE-suppresses-prostate-cancer-metastasis
#3
Anthony Atala
No abstract text is available yet for this article.
December 2017: Journal of Urology
https://www.readbyqxmd.com/read/29141666/intron-retention-enhances-gene-regulatory-complexity-in-vertebrates
#4
Ulf Schmitz, Natalia Pinello, Fangzhi Jia, Sultan Alasmari, William Ritchie, Maria-Cristina Keightley, Shaniko Shini, Graham J Lieschke, Justin J-L Wong, John E J Rasko
BACKGROUND: While intron retention (IR) is now widely accepted as an important mechanism of mammalian gene expression control, it remains the least studied form of alternative splicing. To delineate conserved features of IR, we performed an exhaustive phylogenetic analysis in a highly purified and functionally defined cell type comprising neutrophilic granulocytes from five vertebrate species spanning 430 million years of evolution. RESULTS: Our RNA-sequencing-based analysis suggests that IR increases gene regulatory complexity, which is indicated by a strong anti-correlation between the number of genes affected by IR and the number of protein-coding genes in the genome of individual species...
November 16, 2017: Genome Biology
https://www.readbyqxmd.com/read/29138281/a-conserved-cytoskeletal-signaling-cascade-mediates-neurotoxicity-of-ftdp-17-tau-mutations-in-vivo
#5
Farah H Bardai, Liqun Wang, Yamini Mutreja, Mythili Yenjerla, T Chris Gamblin, Mel B Feany
The microtubule binding protein tau is strongly implicated in multiple neurodegenerative disorders, including frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), which is caused by mutations in tau. In vitro, FTDP-17 mutant versions of tau can reduce microtubule binding and increase aggregation of tau, but the mechanism by which these mutations promote disease in vivo is not clear. Here we take a combined biochemical and in vivo modeling approach to define functional properties of tau driving neurotoxicity in vivo We express wild type human tau and five FTDP-17 mutant forms of tau in Drosophila using a site-directed insertion strategy to ensure equivalent levels of expression...
November 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29134405/cell-type-specific-gene-expression-patterns-in-the-knee-cartilage-in-an-osteoarthritis-rat-model
#6
Michal Korostynski, Natalia Malek, Marcin Piechota, Katarzyna Starowicz
Osteoarthritis (OA) is a chronic degenerative disease that leads to joint failure, pain, and disability. Gene regulation is implicated as a driver of the imbalance between the expression of catabolic and anabolic factors that eventually leads to the degeneration of osteoarthritic cartilage. In our model, knee-joint OA was induced in male Wistar rats by intra-articular sodium monoiodoacetate (MIA) injections. Whole-genome microarrays were used to analyse the alterations in gene expression during the time-course of OA development (at 2, 14, and 28 days post-injection) in rat knee joints...
November 13, 2017: Functional & Integrative Genomics
https://www.readbyqxmd.com/read/29131020/androgen-triggers-the-pro-migratory-cxcl12-cxcr4-axis-in-ar-positive-breast-cancer-cell-lines-underlying-mechanism-and-possible-implications-for-the-use-of-aromatase-inhibitors-in-breast-cancer
#7
Kalliopi Azariadis, Fotini Kiagiadaki, Vasiliki Pelekanou, Vasiliki Bempi, Kostas Alexakis, Marilena Kampa, Andreas Tsapis, Elias Castanas, George Notas
BACKGROUND/AIMS: Reports regarding the role of androgen in breast cancer (BC) are conflicting. Some studies suggest that androgen could lead to undesirable responses in the presence of certain BC tumor characteristics. We have shown that androgen induces C-X-C motif chemokine 12 (CXCL12) in BC cell lines. Our aim was to identify the mechanisms regulating the phenotypic effects of androgen-induced CXCL12 on Androgen Receptor (AR) positive BC cell lines. METHODS: We analyzed the expression of CXCL12 and its receptors with qPCR and ELISA and the role of Nuclear Receptor Coactivator 1 (NCOA1) in this effect...
November 3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29127741/plpa-a-pilz-like-protein-regulates-directed-motility-of-the-bacterium-myxococcus-xanthus
#8
Connor B Pogue, Tianyi Zhou, Beiyan Nan
The rod-shaped bacterium Myxococcus xanthus moves on surfaces along its long cell axis and reverses its moving direction regularly. Current models propose that the asymmetric localization of a Ras-like GTPase, MglA, to leading cell poles determines the moving direction of cells. However, cells are still motile in the mutants where MglA localizes symmetrically, suggesting the existence of additional regulators that control moving direction. In this study, we identified PlpA, a PilZ-like protein that regulates the direction of motility...
November 11, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/29126713/turmeric-curcuma-longa-mirnas-and-their-regulating-targets-are-involved-in-development-and-secondary-metabolite-pathways
#9
Noopur Singh, Ashok Sharma
Turmeric has been used as a therapeutic herb over centuries in traditional medicinal systems due to the presence of several secondary metabolite compounds. microRNAs are known to regulate gene expression at the post-transcriptional level by transcriptional cleavage or translation repression. miRNAs have been demonstrated to play an active role in secondary metabolism regulation. The present work was focused on the identification of the miRNAs involved in the regulation of secondary metabolite and development process of turmeric...
November 7, 2017: Comptes Rendus Biologies
https://www.readbyqxmd.com/read/29120410/molecular-analysis-of-axonal-intrinsic-and-glial-associated-co-regulation-of-axon-degeneration
#10
Alejandra Catenaccio, Maica Llavero Hurtado, Paula Diaz, Douglas J Lamont, Thomas M Wishart, Felipe A Court
Wallerian degeneration is an active program tightly associated with axonal degeneration, required for axonal regeneration and functional recovery after nerve damage. Here we provide a functional molecular foundation for our undertstanding of the complex non-cell autonomous role of glial cells in the regulation of axonal degeneration. To shed light on the complexity of the molecular machinery governing axonal degeneration we employ a multi-model, unbiased, in vivo approach combining morphological assesment and quantitative proteomics with in silico-based higher order functional clustering to genetically uncouple the intrinsic and extrinsic processes governing Wallerian degeneration...
November 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29117471/tumor-adjacent-tissue-co-expression-profile-analysis-reveals-pro-oncogenic-ribosomal-gene-signature-for-prognosis-of-resectable-hepatocellular-carcinoma
#11
O V Grinchuk, S P Yenamandra, R Iyer, M Singh, H K Lee, K H Lim, P K H Chow, V A Kuznetsov
Currently, molecular markers are not used whilst determining the prognosis and treatment strategy for patients with hepatocellular carcinoma (HCC). Here, we proposed that the identification of common pro-oncogenic pathways in primary tumors (PT), and adjacent non-malignant tissues (AT), that typically used to predict HCC patient risks may result in HCC biomarker discovery. We examined the genome-wide mRNA expression profiles of paired PT and AT samples from 321 HCC patients. The workflow integrated differentially expressed gene selection, gene ontology enrichment, computational classification, survival predictions, image analysis and experimental validation methods...
November 8, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29110358/temporal-variation-in-brain-transcriptome-is-associated-with-the-expression-of-female-mimicry-as-a-sequential-male-alternative-reproductive-tactic-in-fish
#12
Sara D Cardoso, David Gonçalves, Alexander Goesmann, Adelino V M Canário, Rui F Oliveira
Distinct patterns of gene expression often underlie intra- and inter-sexual differences, and the study of this set of co-regulated genes is essential to understand the emergence of complex behavioural phenotypes. Here, we describe the development of a de novo transcriptome and brain gene expression profiles of wild-caught peacock blenny, Salaria pavo, an intertidal fish with sex-role reversal in courtship behaviour (i.e. females are the courting sex) and sequential alternative reproductive tactics in males (i...
November 7, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/29109785/overexpression-of-mir-194-reverses-hmga2-driven-signatures-in-colorectal-cancer
#13
Hsin-Yi Chang, Shu-Ping Ye, Shiow-Lin Pan, Tzu-Ting Kuo, Bia Chia Liu, Yi-Lin Chen, Tsui-Chin Huang
Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide with increasing incidence and mortality in developed countries. Oncogenes and microRNAs regulate key signaling pathways in CRC and are known to be deregulated. Oncogenic transcriptional regulator high-mobility group AT-hook 2 (HMGA2) participates in the transformation of several cancers including CRC and exhibits strong correlation with poor prognosis and distal metastasis. Evidence of HMGA2 and its co-regulated miRs contributing to tumor progression remains to be clarified...
2017: Theranostics
https://www.readbyqxmd.com/read/29106954/the-ascorbate-peroxidase-apx1-is-a-direct-target-of-a-zinc-finger-transcription-factor-zfp36-and-a-late-embryogenesis-abundant-protein-oslea5-interacts-with-zfp36-to-co-regulate-osapx1-in-seed-germination-in-rice
#14
Liping Huang, Jing Jia, Xixi Zhao, MengYao Zhang, Xingxiu Huang, E Ji, Lan Ni, Mingyi Jiang
Seed germination is a vital developmental process. Abscisic acid (ABA) is an essential repressor of seed germination, while ROS (reactive oxygen species) also plays a vital role in regulating seed germination. ABA could inhibit the production of ROS in seed germination, but the mechanism of ABA reduced ROS production in seed germination was hitherto unknown. Here, by ChIP (chromatin immunoprecipitation)-seq, we found that ZFP36, a rice zinc finger transcription factor, could directly bind to the promoter of OsAPX1, coding an ascorbate peroxidase (APX) which has the most affinity for H2O2 (substrate; a type of ROS), and act as a transcriptional activator of OsAPX1 promoter...
October 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29106444/automatic-module-selection-from-several-microarray-gene-expression-studies
#15
Alix Zollinger, Anthony C Davison, Darlene R Goldstein
Independence of genes is commonly but incorrectly assumed in microarray data analysis; rather, genes are activated in co-regulated sets referred to as modules. In this article, we develop an automatic method to define modules common to multiple independent studies. We use an empirical Bayes procedure to estimate a sparse correlation matrix for all studies, identify modules by clustering, and develop an extreme-value-based method to detect so-called scattered genes, which do not belong to any module. The resulting algorithm is very fast and produces accurate modules in simulation studies...
July 1, 2017: Biostatistics
https://www.readbyqxmd.com/read/29106399/a-microrna-screen-reveals-that-elevated-hepatic-ectodysplasin-a-expression-contributes-to-obesity-induced-insulin-resistance-in-skeletal-muscle
#16
Motoharu Awazawa, Paula Gabel, Eva Tsaousidou, Hendrik Nolte, Marcus Krüger, Joel Schmitz, P Justus Ackermann, Claus Brandt, Janine Altmüller, Susanne Motameny, F Thomas Wunderlich, Jan-Wilhelm Kornfeld, Matthias Blüher, Jens C Brüning
Over 40% of microRNAs (miRNAs) are located in introns of protein-coding genes, and many of these intronic miRNAs are co-regulated with their host genes. In such cases of co-regulation, the products of host genes and their intronic miRNAs can cooperate to coordinately regulate biologically important pathways. Therefore, we screened intronic miRNAs dysregulated in the livers of mouse models of obesity to identify previously uncharacterized protein-coding host genes that may contribute to the pathogenesis of obesity-associated insulin resistance and type 2 diabetes mellitus...
November 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29104906/the-co-regulation-data-harvester-automating-gene-annotation-starting-from-a-transcriptome-database
#17
Lev M Tsypin, Aaron P Turkewitz
Identifying co-regulated genes provides a useful approach for defining pathway-specific machinery in an organism. To be efficient, this approach relies on thorough genome annotation, a process much slower than genome sequencing per se. Tetrahymena thermophila, a unicellular eukaryote, has been a useful model organism and has a fully sequenced but sparsely annotated genome. One important resource for studying this organism has been an online transcriptomic database. We have developed an automated approach to gene annotation in the context of transcriptome data in T...
2017: SoftwareX
https://www.readbyqxmd.com/read/29101280/an-arabidopsis-glycine-rich-plasma-membrane-protein-enhances-disease-resistance-in-soybean
#18
Bing Wang, Rishi Sumit, Binod B Sahu, Micheline N Ngaki, Subodh K Srivastava, Yang Yang, Madan K Bhattacharyya
Nonhost resistance is defined as the immunity of a plant species to all nonadapted pathogen species. Arabidopsis ecotype Columbia-0 (Col-0) is nonhost to oomycete plant pathogen Phytophthora sojae and fungal plant pathogen Fusarium virguliforme that are pathogenic to soybean. Previously, we reported generating pss1 mutation in the pen1-1 genetic background, genetic mapping and characterization of the Arabidopsis nonhost resistance Phytophthora sojae susceptible gene locus, PSS1. In this study, we identified six candidate PSS1 genes by comparing single nucleotide polymorphisms (SNPs) of (i) the bulked DNA sample of seven F2:3 families homozygous for the pss1 allele and (ii) the pen1-1 mutant with Col-0...
November 3, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29101097/the-tripartite-motif-containing-24-acts-as-a-novel-coactivator-of-the-constitutive-active-androstane-receptor
#19
Yuichiro Kanno, Yuki Kure, Saori Kobayashi, Mariko Mizuno, Yumi Tsuchiya, Naoya Yamashita, Kiyomitsu Nemoto, Yoshio Inouye
The constitutive active/androstane receptor (CAR) is a nuclear receptor that acts as a transcription factor for a variety of genes, including genes encoding xenobiotic, steroid and drug-metabolizing enzymes and transporters. Transactivation of a target gene by a transcription factor is generally mediated through the concerted and stepwise recruitment of various proteins termed co-regulators, including coactivators and corepressors. In this study, tripartite motif containing 24 (TRIM24; also known as transcriptional intermediary factor 1 alpha) was found to interact with the CAR...
November 3, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29095861/identification-of-proteins-associated-with-clinical-and-pathological-features-of-proliferative-diabetic-retinopathy-in-vitreous-and-fibrovascular-membranes
#20
Ingeborg Klaassen, Ewout W de Vries, Ilse M C Vogels, Antoine H C van Kampen, Machteld I Bosscha, David H W Steel, Cornelis J F Van Noorden, Sarit Y Lesnik-Oberstein, Reinier O Schlingemann
PURPOSE: To identify the protein profiles in vitreous associated with retinal fibrosis, angiogenesis, and neurite formation in epiretinal fibrovascular membranes (FVMs) in patients with proliferative diabetic retinopathy (PDR). METHODS: Vitreous samples of 5 non-diabetic control patients with vitreous debris and 7 patients with PDR membranes were screened for 507 preselected proteins using the semi-quantitative RayBio® L-series 507 antibody array. From this array, 60 proteins were selected for a custom quantitative antibody array (Raybiotech, Human Quantibody® array), analyzing 7 control patients, 8 PDR patients with FVMs, and 5 PDR patients without FVMs...
2017: PloS One
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