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https://www.readbyqxmd.com/read/28429447/using-the-realist-perspective-to-link-theory-from-qualitative-evidence-synthesis-to-quantitative-studies-broadening-the-matrix-approach
#1
Leonie van Grootel, Floryt van Wesel, Alison O'Mara-Eves, James Thomas, Joop Hox, Hennie Boeije
BACKGROUND: This study describes an approach for the use of a specific type of qualitative evidence synthesis in the matrix approach, a mixed studies reviewing method. The matrix approach compares quantitative and qualitative data on the review level by juxtaposing concrete recommendations from the qualitative evidence synthesis against interventions in primary quantitative studies. However, types of qualitative evidence syntheses that are associated with theory building generate theoretical models instead of recommendations...
April 21, 2017: Research Synthesis Methods
https://www.readbyqxmd.com/read/28423671/genome-wide-dna-methylation-analysis-reveals-molecular-subtypes-of-pancreatic-cancer
#2
Nitish Kumar Mishra, Chittibabu Guda
Pancreatic cancer (PC) is the fourth leading cause of cancer deaths in the United States with a five-year patient survival rate of only 6%. Early detection and treatment of this disease is hampered due to lack of reliable diagnostic and prognostic markers. Recent studies have shown that dynamic changes in the global DNA methylation and gene expression patterns play key roles in the PC development; hence, provide valuable insights for better understanding the initiation and progression of PC. In the current study, we used DNA methylation, gene expression, copy number, mutational and clinical data from pancreatic patients...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423659/targeting-hox-pbx-dimers-in-cancer
#3
REVIEW
Richard Morgan, Mohamed El-Tanani, Keith D Hunter, Kevin J Harrington, Hardev S Pandha
The HOX and PBX gene families encode transcription factors that have key roles in establishing the identity of cells and tissues in early development. Over the last 20 years it has become apparent that they are also dysregulated in a wide range of solid and haematological malignancies and have a predominantly pro-oncogenic function. A key mode of transcriptional regulation by HOX and PBX proteins is through their interaction as a heterodimer or larger complex that enhances their binding affinity and specificity for DNA, and there is growing evidence that this interaction is a potential therapeutic target in malignancies that include prostate, breast, renal, ovarian and lung cancer, melanoma, myeloma, and acute myeloid leukaemia...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420874/therapeutic-targeting-using-tumor-specific-peptides-inhibits-long-non-coding-rna-hotair-activity-in-ovarian-and-breast-cancer
#4
Ali R Özeş, Yinu Wang, Xingyue Zong, Fang Fang, Jay Pilrose, Kenneth P Nephew
Long non-coding RNAs (lncRNAs) play key roles in human diseases, including cancer. Functional studies of the lncRNA HOTAIR (HOX transcript antisense RNA) provide compelling evidence for therapeutic targeting of HOTAIR in cancer, but targeting lncRNAs in vivo has proven to be difficult. In the current study, we describe a peptide nucleic acids (PNA)-based approach to block the ability of HOTAIR to interact with EZH2 and subsequently inhibit HOTAIR-EZH2 activity and resensitize resistant ovarian tumors to platinum...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28415631/lncrna-hotair-acts-a-competing-endogenous-rna-to-control-the-expression-of-notch3-via-sponging-mir-613-in-pancreatic-cancer
#5
Huihua Cai, Jie Yao, Yong An, Xuemin Chen, Weibo Chen, Di Wu, Boyang Luo, Yong Yang, Yong Jiang, Donglin Sun, Xiaozhou He
Pancreatic cancer is one of the most deadly cancers with a poor prognosis. Though studies have implicated the roles of microRNAs in pancreatic cancer progression, little is known about the role of miR-613 in pancreatic cancer. In the present study, the expression of miR-613 was down-regulated in pancreatic cancer tissues and cancer cell lines. Down-regulation of miR-613 was positively correlated with tumor differentiation, advanced TNM stage, nodal metastasis and shorter overall survival in patients with pancreatic cancer...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414802/neuronal-cell-fate-specification-by-the-molecular-convergence-of-different-spatio-temporal-cues-on-a-common-initiator-terminal-selector-gene
#6
Johannes Stratmann, Stefan Thor
The extensive genetic regulatory flows underlying specification of different neuronal subtypes are not well understood at the molecular level. The Nplp1 neuropeptide neurons in the developing Drosophila nerve cord belong to two sub-classes; Tv1 and dAp neurons, generated by two distinct progenitors. Nplp1 neurons are specified by spatial cues; the Hox homeotic network and GATA factor grn, and temporal cues; the hb -> Kr -> Pdm -> cas -> grh temporal cascade. These spatio-temporal cues combine into two distinct codes; one for Tv1 and one for dAp neurons that activate a common terminal selector feedforward cascade of col -> ap/eya -> dimm -> Nplp1...
April 17, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28404743/nuclear-complex-of-glyceraldehyde-3-phosphate-dehydrogenase-and-dna-repair-enzyme-apurinic-apyrimidinic-endonuclease-i-protect-smooth-muscle-cells-against-oxidant-induced-cell-death
#7
Xuwei Hou, Patricia Snarski, Yusuke Higashi, Tadashi Yoshida, Alexander Jurkevich, Patrick Delafontaine, Sergiy Sukhanov
Atherosclerotic plaque destabilization is the major determinant of most acute coronary events. Smooth muscle cell (SMC) death contributes to plaque destabilization. Here, we describe a novel antiapoptotic mechanism in vascular SMC that involves interaction of nuclear glyceraldehyde-3-phosphate dehydrogenase (GAPDH) with apurinic/apyrimidinic endonuclease 1 (Ape1), the major oxidized DNA repair enzyme. GAPDH down-regulation potentiated H2O2-induced DNA damage and SMC apoptosis. Conversely, GAPDH overexpression decreased DNA damage and protected SMCs against apoptosis...
April 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28402266/expression-signatures-of-hox-cluster-genes-in-cervical-cancer-pathogenesis-impact-of-human-papillomavirus-type-16-oncoprotein-e7
#8
Sweta Sharma Saha, Rahul Roy Chowdhury, Nidhu Ranjan Mondal, Sudipta Roy, Sharmila Sengupta
The Homeobox (HOX) genes encode important transcription factors showing deregulated expression in several cancers. However, their role in cervical cancer pathogenesis, remains largely unexplored. Herein, we studied their association with Human Papillomavirus type 16 (HPV16) mediated cervical cancers. Our previously published gene expression microarray data revealed a significant alteration of 12 out of 39 HOX cluster members among cervical cancer cases, in comparison to the histopathologically normal controls...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28399410/hoxa9-and-meis1-cooperatively-induce-addiction-to-syk-signaling-by-suppressing-mir-146a-in-acute-myeloid-leukemia
#9
Sebastian Mohr, Carmen Doebele, Federico Comoglio, Tobias Berg, Julia Beck, Hanibal Bohnenberger, Gabriela Alexe, Jasmin Corso, Philipp Ströbel, Astrid Wachter, Tim Beissbarth, Frank Schnütgen, Anjali Cremer, Nadine Haetscher, Stefanie Göllner, Arefeh Rouhi, Lars Palmqvist, Michael A Rieger, Timm Schroeder, Halvard Bönig, Carsten Müller-Tidow, Florian Kuchenbauer, Ekkehard Schütz, Anthony R Green, Henning Urlaub, Kimberly Stegmaier, R Keith Humphries, Hubert Serve, Thomas Oellerich
The transcription factor Meis1 drives myeloid leukemogenesis in the context of Hox gene overexpression but is currently considered undruggable. We therefore investigated whether myeloid progenitor cells transformed by Hoxa9 and Meis1 become addicted to targetable signaling pathways. A comprehensive (phospho)proteomic analysis revealed that Meis1 increased Syk protein expression and activity. Syk upregulation occurs through a Meis1-dependent feedback loop. By dissecting this loop, we show that Syk is a direct target of miR-146a, whose expression is indirectly regulated by Meis1 through the transcription factor PU...
April 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28399140/collinear-hox-hox-interactions-are-involved-in-patterning-the-vertebrate-anteroposterior-a-p-axis
#10
Kongju Zhu, Herman P Spaink, Antony J Durston
Investigating regulation and function of the Hox genes, key regulators of positional identity in the embryo, opened a new vista in developmental biology. One of their most striking features is collinearity: the temporal and spatial orders of expression of these clustered genes each match their 3' to 5' order on the chromosome. Despite recent progress, the mechanisms underlying collinearity are not understood. Here we show that ectopic expression of 4 different single Hox genes predictably induces and represses expression of others, leading to development of different predictable specific sections of the body axis...
2017: PloS One
https://www.readbyqxmd.com/read/28394464/novel-mca-id-syndrome-with-ash1l-mutation
#11
Nobuhiko Okamoto, Fuyuki Miya, Tatsuhiko Tsunoda, Mitsuhiro Kato, Shinji Saitoh, Mami Yamasaki, Yonehiro Kanemura, Kenjiro Kosaki
We identified a novel mutation in ASH1L in a patient with severe intellectual disability, growth failure, microcephaly, facial dysmorphism, myelination delay, and skeletal abnormalities. ASH1L is a histone methyltransferase that associates with the transcribed region of all active genes examined, including Hox genes. It catalyzes H3K36 methylation and plays important roles in development. There has been increasing evidence that heterozygous mutation of ASH1L is associated with ID and autism spectrum disorders...
April 10, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28392108/anterior-posterior-gradient-in-neural-stem-and-daughter-cell-proliferation-governed-by-spatial-and-temporal-hox-control
#12
Ignacio Monedero Cobeta, Behzad Yaghmaeian Salmani, Stefan Thor
A readily evident feature of animal central nervous systems (CNSs), apparent in all vertebrates and many invertebrates alike, is its "wedge-like" appearance, with more cells generated in anterior than posterior regions. This wedge could conceivably be established by an antero-posterior (A-P) gradient in the number of neural progenitor cells, their proliferation behaviors, and/or programmed cell death (PCD). However, the contribution of each of these mechanisms, and the underlying genetic programs, are not well understood...
March 30, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28386341/hoxb9-promotes-the-migration-and-invasion-via-tgf-%C3%AE-1-smad2-slug-signaling-pathway-in-oral-squamous-cell-carcinoma
#13
Mei Xue, Fei-Ya Zhu, Lin Chen, Kai Wang
HoxB9, as a HOX family member, is known to play important roles in embryonic development. Recent studies have shown that HoxB9 is involved in cancer progression. However, little is known about the role of HoxB9 and the underlying mechanisms that suppress oral squamous cell carcinoma (OSCC) progression. In the present study, we used immunohistochemical staining to demonstrate that HoxB9 is over-expressed in OSCC cells and found that high levels of HoxB9 were significantly associated with shorter overall survival in patients with OSCC...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28384324/psip1-p52-regulates-posterior-hoxa-genes-through-activation-of-lncrna-hottip
#14
Madapura M Pradeepa, Fionnuala McKenna, Gillian C A Taylor, Hemant Bengani, Graeme R Grimes, Andrew J Wood, Shipra Bhatia, Wendy A Bickmore
Long noncoding RNAs (lncRNAs) have been implicated in various biological functions including the regulation of gene expression, however, the functionality of lncRNAs is not clearly understood and conflicting conclusions have often been reached when comparing different methods to investigate them. Moreover, little is known about the upstream regulation of lncRNAs. Here we show that the short isoform (p52) of a transcriptional co-activator-PC4 and SF2 interacting protein (Psip1), which is known to be involved in linking transcription to RNA processing, specifically regulates the expression of the lncRNA Hottip-located at the 5' end of the Hoxa locus...
April 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28380363/polycomb-and-hox-genes-control-jnk-induced-remodeling-of-the-segment-boundary-during-drosophila-morphogenesis
#15
Solange Roumengous, Raphaël Rousset, Stéphane Noselli
In segmented tissues, anterior and posterior compartments represent independent morphogenetic domains, which are made of distinct lineages separated by boundaries. During dorsal closure of the Drosophila embryo, specific "mixer cells" (MCs) are reprogrammed in a JNK-dependent manner to express the posterior determinant engrailed (en) and cross the segment boundary. Here, we show that JNK signaling induces de novo expression of en in the MCs through repression of Polycomb (Pc) and release of the en locus from the silencing PcG bodies...
April 4, 2017: Cell Reports
https://www.readbyqxmd.com/read/28380068/mouse-fitness-measures-reveal-incomplete-functional-redundancy-of-hox-paralogous-group-1-proteins
#16
James S Ruff, Raed B Saffarini, Leda L Ramoz, Linda C Morrison, Shambralyn Baker, Sean M Laverty, Petr Tvrdik, Mario R Capecchi, Wayne K Potts
Here we assess the fitness consequences of the replacement of the Hoxa1 coding region with its paralog Hoxb1 in mice (Mus musculus) residing in semi-natural enclosures. Previously, this Hoxa1B1 swap was reported as resulting in no discernible embryonic or physiological phenotype (i.e., functionally redundant), despite the 51% amino acid sequence differences between these two Hox proteins. Within heterozygous breeding cages no differences in litter size nor deviations from Mendelian genotypic expectations were observed in the outbred progeny; however, within semi-natural population enclosures mice homozygous for the Hoxa1B1 swap were out-reproduced by controls resulting in the mutant allele being only 87...
2017: PloS One
https://www.readbyqxmd.com/read/28377584/rotiferan-hox-genes-give-new-insights-into-the-evolution-of-metazoan-bodyplans
#17
Andreas C Fröbius, Peter Funch
The phylum Rotifera consists of minuscule, nonsegmented animals with a unique body plan and an unresolved phylogenetic position. The presence of pharyngeal articulated jaws supports an inclusion in Gnathifera nested in the Spiralia. Comparison of Hox genes, involved in animal body plan patterning, can be used to infer phylogenetic relationships. Here, we report the expression of five Hox genes during embryogenesis of the rotifer Brachionus manjavacas and show how these genes define different functional components of the nervous system and not the usual bilaterian staggered expression along the anteroposterior axis...
April 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28376832/serum-hotair-as-a-novel-diagnostic-biomarker-for-esophageal-squamous-cell-carcinoma
#18
Wenjian Wang, Xiaotian He, Zehua Zheng, Xiaofan Ma, Xueting Hu, Duoguang Wu, Minghui Wang
BACKGROUND: Early diagnosis of esophageal squamous cell carcinoma (ESCC) is an important issue to improve the prognosis. HOX transcript antisense RNA (HOTAIR), a long noncoding RNA (lncRNA) expressed from the HOXC locus, has been recently revealed as an oncogenic regulator in ESCC. This study aimed to investigate whether serum HOTAIR is involved in the diagnosis of ESCC. METHODS: In this study, we detected serum HOTAIR expression in 50 patients with ESCC (including 42 tumor resection and 8 without surgery) and 20 healthy volunteers to investigate the role of serum HOTAIR in ESCC using the quantitative real-time polymerase chain reaction (qRT-PCR) method...
April 4, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28366456/in%C3%A2-vitro-generation-of-vascular-wall-resident-multipotent-stem-cells-of%C3%A2-mesenchymal-nature-from-murine-induced-pluripotent-stem-cells
#19
Jennifer Steens, Melanie Zuk, Mohamed Benchellal, Lea Bornemann, Nadine Teichweyde, Julia Hess, Kristian Unger, André Görgens, Hannes Klump, Diana Klein
The vascular wall (VW) serves as a niche for mesenchymal stem cells (MSCs). In general, tissue-specific stem cells differentiate mainly to the tissue type from which they derive, indicating that there is a certain code or priming within the cells as determined by the tissue of origin. Here we report the in vitro generation of VW-typical MSCs from induced pluripotent stem cells (iPSCs), based on a VW-MSC-specific gene code. Using a lentiviral vector expressing the so-called Yamanaka factors, we reprogrammed tail dermal fibroblasts from transgenic mice containing the GFP gene integrated into the Nestin-locus (NEST-iPSCs) to facilitate lineage tracing after subsequent MSC differentiation...
April 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28363633/high-resolution-methylation-analysis-of-the-hoxa5-regulatory-region-in-different-somatic-tissues-of-laboratory-mouse-during-development
#20
Puja Sinha, Kiran Singh, Manisha Sachan
Homeobox genes encode a group of DNA binding regulatory proteins whose key function occurs in the spatial-temporal organization of genome during embryonic development and differentiation. The role of these Hox genes during ontogenesis makes it an important model for research. HoxA5 is a member of Hox gene family playing a central role during axial body patterning and morphogenesis. DNA modification studies have shown that the function of Hox genes is partly governed by the methylation-mediated gene expression regulation...
January 2017: Gene Expression Patterns: GEP
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