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Leonel Armas-López, Patricia Piña-Sánchez, Oscar Arrieta, Enrique Guzman de Alba, Blanca Ortiz-Quintero, Patricio Santillán-Doherty, David C Christiani, Joaquín Zúñiga, Federico Ávila-Moreno
Several homeobox-related gene (HOX) transcription factors such as mesenchyme HOX-2 (MEOX2) have previously been associated with cancer drug resistance, malignant progression and/or clinical prognostic responses in lung cancer patients; however, the mechanisms involved in these responses have yet to be elucidated. Here, an epigenomic strategy was implemented to identify novel MEOX2 gene promoter transcription targets and propose a new molecular mechanism underlying lung cancer drug resistance and poor clinical prognosis...
May 9, 2017: Oncotarget
Bongyong Lee, Anupama Sahoo, John Marchica, Erwin Holzhauser, Xiaoli Chen, Jian-Liang Li, Tatsuya Seki, Subramaniam Shyamala Govindarajan, Fatu Badiane Markey, Mona Batish, Sonali J Lokhande, Shaojie Zhang, Animesh Ray, Ranjan J Perera
Molecular mechanisms by which long noncoding RNA (lncRNA) molecules may influence cancerous condition are poorly understood. The aberrant expression of SPRIGHTLY lncRNA, encoded within the drosophila gene homolog Sprouty-4 intron, is correlated with a variety of cancers, including human melanomas. We demonstrate by SHAPE-seq and dChIRP that SPRIGHTLY RNA secondary structure has a core pseudoknotted domain. This lncRNA interacts with the intronic regions of six pre-mRNAs: SOX5, SMYD3, SND1, MEOX2, DCTN6, and RASAL2, all of which have cancer-related functions...
May 2017: Science Advances
Moe Kitazawa, Masaru Tamura, Tomoko Kaneko-Ishino, Fumitoshi Ishino
Paternally expressed 11/Retrotransposon-like 1 (Peg11/Rtl1) knockout (KO) mice show mid- to late fetal lethality or late fetal growth retardation associated with frequent neonatal lethality. The lethal phenotype is largely dependent on genetic background and becomes more severe with each succeeding generation in the course of backcross experiments to C57BL/6 (B6). We previously suggested that these lethal and growth phenotypes in the fetal stages were due to severe defects in placental fetal capillaries in the labyrinth layer...
February 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Cassandra R Gohn, Emily K Blue, BreAnn M Sheehan, Kaela M Varberg, Laura S Haneline
Diabetes mellitus (DM) during pregnancy has long-lasting implications for the fetus, including cardiovascular morbidity. Previously, we showed that endothelial colony forming cells (ECFCs) from DM human pregnancies have decreased vasculogenic potential. Here, we evaluate whether the molecular mechanism responsible for this phenotype involves the transcription factor, Mesenchyme Homeobox 2 (MEOX2). In human umbilical vein endothelial cells, MEOX2 upregulates cyclin-dependent kinase inhibitor expression, resulting in increased senescence and decreased proliferation...
July 2017: Journal of Cellular Physiology
Ping Liu, Fei Yang, Yu Zhuang, Qingyang Xiao, Huabin Cao, Caiying Zhang, Tiancheng Wang, Huayuan Lin, Xiaoquan Guo, Guoliang Hu
Ascites syndrome (AS), also known as pulmonary artery hypertension, remains a challenging disease that severely affects both humans and broiler chickens. Pulmonary artery remodeling presents a key step in the development of AS. In this study, we obtained pulmonary artery tissues from broilers with and without AS to perform miRNA sequencing analysis, miRNA-mRNA association analysis and pathological examinations. 29 significantly differentially expressed miRNAs were found both in known and novel miRNAs with 18 up-regulated and 11 down-regulated miRNAs...
January 10, 2017: Oncotarget
Chunhui Xie, Kai Shi, Xi Zhang, Jingchun Zhao, Jiaao Yu
The cell biological basis for scar formation is mainly via excessive fibroblast proliferation accompanied by hypernomic Col I accumulation and inflammation. The role of miR-1908 in scar formation has not been investigated. In this study, we found that miR-1908 expression was inversely associated with the scar suppressor Ski in normal, burn-wounded, healing and scar dermal tissues in humans. Bioinformatics and luciferase reporter gene assays confirmed that miR-1908 targeted the 3'UTR region of Ski mRNA and suppressed Ski expression...
November 2016: Cell and Tissue Research
Ileana Soto, Weronika A Grabowska, Kristen D Onos, Leah C Graham, Harriet M Jackson, Stephen N Simeone, Gareth R Howell
Evidence suggests that multiple genetic and environmental factors conspire together to increase susceptibility to Alzheimer's disease (AD). The amyloid cascade hypothesis states that deposition of the amyloid-β (Aβ) peptide is central to AD; however, evidence in humans and animals suggests that Aβ buildup alone is not sufficient to cause neuronal cell loss and cognitive decline. Mouse models that express high levels of mutant forms of amyloid precursor protein and/or cleaving enzymes deposit amyloid but do not show neuron loss...
June 2016: Neurobiology of Aging
(no author information available yet)
No abstract text is available yet for this article.
April 2016: Experimental and Molecular Pathology
Federico Ávila-Moreno, Leonel Armas-López, Aldo M Álvarez-Moran, Zoila López-Bujanda, Blanca Ortiz-Quintero, Alfredo Hidalgo-Miranda, Francisco Urrea-Ramírez, R María Rivera-Rosales, Eugenia Vázquez-Manríquez, Erika Peña-Mirabal, José Morales-Gómez, Juan C Vázquez-Minero, José L Téllez-Becerra, Roberto Ramírez-Mendoza, Alejandro Ávalos-Bracho, Enrique Guzmán de Alba, Karla Vázquez-Santillán, Vilma Maldonado-Lagunas, Patricio Santillán-Doherty, Patricia Piña-Sánchez, Joaquin Zúñiga-Ramos
No abstract text is available yet for this article.
2016: PloS One
Maïté Noizet, Emilie Lagoutte, Marlène Gratigny, Marielle Bouschbacher, Isabelle Lazareth, Hugues Roest Crollius, Xavier Darzacq, Claire Dugast-Darzacq
Fibroblasts are important players in regulating tissue homeostasis. In the dermis, they are involved in wound healing where they differentiate into contractile myofibroblasts leading to wound closure. In nonhealing chronic wounds, fibroblasts fail to undertake differentiation. We established and used a human ex vivo model of chronic wounds where fibroblasts can undergo normal myofibroblast differentiation, or take on a nondifferentiable pathological state. At the whole genome scale, we identified the genes that are differentially regulated in these two cell fates...
March 2016: Wound Repair and Regeneration
Philippe Daubas, Nathalie Duval, Lola Bajard, Francina Langa Vives, Benoît Robert, Baljinder S Mankoo, Margaret Buckingham
Skeletal myogenesis in vertebrates is initiated at different sites of skeletal muscle formation during development, by activation of specific control elements of the myogenic regulatory genes. In the mouse embryo, Myf5 is the first myogenic determination gene to be expressed and its spatiotemporal regulation requires multiple enhancer sequences, extending over 120 kb upstream of the Mrf4-Myf5 locus. An enhancer, located at -57/-58 kb from Myf5, is responsible for its activation in myogenic cells derived from the hypaxial domain of the somite, that will form limb muscles...
November 4, 2015: Biology Open
Wen-Yi Yang, Thibault Petit, Lutgarde Thijs, Zhen-Yu Zhang, Lotte Jacobs, Azusa Hara, Fang-Fei Wei, Erika Salvi, Lorena Citterio, Simona Delli Carpini, Yu-Mei Gu, Judita Knez, Nicholas Cauwenberghs, Matteo Barcella, Cristina Barlassina, Paolo Manunta, Giulia Coppiello, Xabier L Aranguren, Tatiana Kuznetsova, Daniele Cusi, Peter Verhamme, Aernout Luttun, Jan A Staessen
BACKGROUND: In mice MEOX2/TCF15 heterodimers are highly expressed in heart endothelial cells and are involved in the transcriptional regulation of lipid transport. In a general population, we investigated whether genetic variation in these genes predicted coronary heart disease (CHD). RESULTS: In 2027 participants randomly recruited from a Flemish population (51.0 % women; mean age 43.6 years), we genotyped six SNPs in MEOX2 and four in TCF15. Over 15.2 years (median), CHD, myocardial infarction, coronary revascularisation and ischaemic cardiomyopathy occurred in 106, 53, 78 and 22 participants...
2015: BMC Genetics
Jennifer Permuth-Wey, Y Ann Chen, Kate Fisher, Susan McCarthy, Xiaotao Qu, Mark C Lloyd, Agnieszka Kasprzak, Michelle Fournier, Vonetta L Williams, Kavita M Ghia, Sean J Yoder, Laura Hall, Christina Georgeades, Funmilayo Olaoye, Kazim Husain, Gregory M Springett, Dung-Tsa Chen, Timothy Yeatman, Barbara Ann Centeno, Jason Klapman, Domenico Coppola, Mokenge Malafa
BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic ductal adenocarcinoma (PDAC) precursors. Differentiating between high-risk IPMNs that warrant surgical resection and low-risk IPMNs that can be monitored is a significant clinical problem, and we sought to discover a panel of mi(cro)RNAs that accurately classify IPMN risk status. METHODOLOGY/PRINCIPAL FINDINGS: In a discovery phase, genome-wide miRNA expression profiling was performed on 28 surgically-resected, pathologically-confirmed IPMNs (19 high-risk, 9 low-risk) using Taqman MicroRNA Arrays...
2015: PloS One
Giulia Coppiello, Maria Collantes, María Salomé Sirerol-Piquer, Sara Vandenwijngaert, Sandra Schoors, Melissa Swinnen, Ine Vandersmissen, Paul Herijgers, Baki Topal, Johannes van Loon, Jan Goffin, Felipe Prósper, Peter Carmeliet, Jose Manuel García-Verdugo, Stefan Janssens, Iván Peñuelas, Xabier L Aranguren, Aernout Luttun
BACKGROUND: Microvascular endothelium in different organs is specialized to fulfill the particular needs of parenchymal cells. However, specific information about heart capillary endothelial cells (ECs) is lacking. METHODS AND RESULTS: Using microarray profiling on freshly isolated ECs from heart, brain, and liver, we revealed a genetic signature for microvascular heart ECs and identified Meox2/Tcf15 heterodimers as novel transcriptional determinants. This signature was largely shared with skeletal muscle and adipose tissue endothelium and was enriched in genes encoding fatty acid (FA) transport-related proteins...
March 3, 2015: Circulation
Mathias Gorski, Adrienne Tin, Maija Garnaas, Gearoid M McMahon, Audrey Y Chu, Bamidele O Tayo, Cristian Pattaro, Alexander Teumer, Daniel I Chasman, John Chalmers, Pavel Hamet, Johanne Tremblay, Marc Woodward, Thor Aspelund, Gudny Eiriksdottir, Vilmundur Gudnason, Tamara B Harris, Lenore J Launer, Albert V Smith, Braxton D Mitchell, Jeffrey R O'Connell, Alan R Shuldiner, Josef Coresh, Man Li, Paul Freudenberger, Edith Hofer, Helena Schmidt, Reinhold Schmidt, Elizabeth G Holliday, Paul Mitchell, Jie Jin Wang, Ian H de Boer, Guo Li, David S Siscovick, Zoltan Kutalik, Tanguy Corre, Peter Vollenweider, Gérard Waeber, Jayanta Gupta, Peter A Kanetsky, Shih-Jen Hwang, Matthias Olden, Qiong Yang, Mariza de Andrade, Elizabeth J Atkinson, Sharon L R Kardia, Stephen T Turner, Jeanette M Stafford, Jingzhong Ding, Yongmei Liu, Cristina Barlassina, Daniele Cusi, Erika Salvi, Jan A Staessen, Paul M Ridker, Harald Grallert, Christa Meisinger, Martina Müller-Nurasyid, Bernhard K Krämer, Holly Kramer, Sylvia E Rosas, Ilja M Nolte, Brenda W Penninx, Harold Snieder, M Fabiola Del Greco, Andre Franke, Ute Nöthlings, Wolfgang Lieb, Stephan J L Bakker, Ron T Gansevoort, Pim van der Harst, Abbas Dehghan, Oscar H Franco, Albert Hofman, Fernando Rivadeneira, Sanaz Sedaghat, André G Uitterlinden, Stefan Coassin, Margot Haun, Barbara Kollerits, Florian Kronenberg, Bernhard Paulweber, Nicole Aumann, Karlhans Endlich, Mike Pietzner, Uwe Völker, Rainer Rettig, Vincent Chouraki, Catherine Helmer, Jean-Charles Lambert, Marie Metzger, Benedicte Stengel, Terho Lehtimäki, Leo-Pekka Lyytikäinen, Olli Raitakari, Andrew Johnson, Afshin Parsa, Murielle Bochud, Iris M Heid, Wolfram Goessling, Anna Köttgen, W H Linda Kao, Caroline S Fox, Carsten A Böger
Genome-wide association studies (GWASs) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, single-nucleotide polymorphisms (SNPs) at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1, and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus, which showed genome-wide significance with an annual change in eGFR...
May 2015: Kidney International
Federico Ávila-Moreno, Leonel Armas-López, Aldo M Álvarez-Moran, Zoila López-Bujanda, Blanca Ortiz-Quintero, Alfredo Hidalgo-Miranda, Francisco Urrea-Ramírez, R María Rivera-Rosales, Eugenia Vázquez-Manríquez, Erika Peña-Mirabal, José Morales-Gómez, Juan C Vázquez-Minero, José L Téllez-Becerra, Roberto Ramírez-Mendoza, Alejandro Ávalos-Bracho, Enrique Guzmán de Alba, Karla Vázquez-Santillán, Vilma Maldonado-Lagunas, Patricio Santillán-Doherty, Patricia Piña-Sánchez, Joaquin Zúñiga-Ramos
Lung cancer is the leading cause of death from malignant diseases worldwide, with the non-small cell (NSCLC) subtype accounting for the majority of cases. NSCLC is characterized by frequent genomic imbalances and copy number variations (CNVs), but the epigenetic aberrations that are associated with clinical prognosis and therapeutic failure remain not completely identify. In the present study, a total of 55 lung cancer patients were included and we conducted genomic and genetic expression analyses, immunohistochemical protein detection, DNA methylation and chromatin immunoprecipitation assays to obtain genetic and epigenetic profiles associated to prognosis and chemoresponse of NSCLC patients...
2014: PloS One
Zhaowei Chen, Wenjing Li, Yan Ning, Tong Liu, Jingxiang Shao, Yaojun Wang
OBJECTIVE: The aim of the present work was to investigate the mechanism of transforming growth factor (TGF)-β1 and Sloan-Kettering Institute (Ski) in the pathogenesis of hypertrophic scars (HS). BACKGROUND: Wound healing is an inherent process, but the aberrant wound healing of skin injury may lead to HS. There has been growing evidence suggesting a role for TGF-β1 and Ski in the pathogenesis of fibrosis. MATERIAL AND METHODS: The MTT assay was used to detect the cell proliferation induced by TGF-β1...
December 2014: Experimental and Molecular Pathology
Ping Liu, Feng Kong, Jue Wang, Qinghua Lu, Haijia Xu, Tonggang Qi, Juan Meng
Perivascular adipocyte (PVAC) proliferation and differentiation were closely involved in cardiovascular disease. We aimed to investigate whether phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways enhance PVAC functions activated by insulin-like growth factor 1(IGF-1) and suppressed by mesenchyme homeobox 2 (MEOX2). In this study, PVACs from primary culture were cultured and induced to differentiate. Cell viability assays demonstrated that IGF-1 promoted PVAC proliferation and differentiation...
February 1, 2015: Experimental Cell Research
Sarah Beck-Cormier, Marie Escande, Céline Souilhol, Sandrine Vandormael-Pournin, Sophie Sourice, Paul Pilet, Charles Babinet, Michel Cohen-Tannoudji
Maintenance of cell survival is essential for proper embryonic development. In the mouse, Notchless homolog 1 (Drosophila) (Nle1) is instrumental for survival of cells of the inner cell mass upon implantation. Here, we analyze the function of Nle1 after implantation using the Meox2(tm1(cre)Sor) mouse that expresses the Cre recombinase specifically in the epiblast at E5.5. First, we find that NLE1 function is required in epiblast cells, as Nle1-deficient cells are rapidly eliminated. In this report, we also show that the Meox2(Cre) transgene is active in specific tissues during organogenesis...
2014: PloS One
Robert Moore, Kathy Qi Cai, Wensi Tao, Elizabeth R Smith, Xiang-Xi Xu
BACKGROUND: Disabled-2 (Dab2) is an endocytic adaptor protein involved in clathrin-mediated endocytosis and cargo trafficking. Since its expression is lost in several cancer types, Dab2 has been suggested to be a tumor suppressor. In vitro studies indicate that Dab2 establishes epithelial cell polarity and organization by directing endocytic trafficking of membrane glycoproteins. Dab2 also modulates cellular signaling pathways by mediating the endocytosis and recycling of surface receptors and associated signaling components...
October 29, 2013: BMC Developmental Biology
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