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https://www.readbyqxmd.com/read/28423671/genome-wide-dna-methylation-analysis-reveals-molecular-subtypes-of-pancreatic-cancer
#1
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
#2
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/28415631/lncrna-hotair-acts-a-competing-endogenous-rna-to-control-the-expression-of-notch3-via-sponging-mir-613-in-pancreatic-cancer
#3
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/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
#4
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
#5
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
#6
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
#7
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/28384324/psip1-p52-regulates-posterior-hoxa-genes-through-activation-of-lncrna-hottip
#8
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/28376832/serum-hotair-as-a-novel-diagnostic-biomarker-for-esophageal-squamous-cell-carcinoma
#9
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/28363633/high-resolution-methylation-analysis-of-the-hoxa5-regulatory-region-in-different-somatic-tissues-of-laboratory-mouse-during-development
#10
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
https://www.readbyqxmd.com/read/28357140/the-noncell-autonomous-requirement-of-proboscipedia-for-growth-and-differentiation-of-the-distal-maxillary-palp-during-metamorphosis-of-drosophila-melanogaster
#11
Anthony Percival-Smith, Gabriel Ponce, Jacob J H Pelling
The Drosophila maxillary palpus that develops during metamorphosis is composed of two elements: the proximal maxillary socket and distal maxillary palp. The HOX protein, Proboscipedia (PB), was required for development of the proximal maxillary socket and distal maxillary palp. For growth and differentiation of the distal maxillary palp, PB was required in the cells of, or close to, the maxillary socket, as well as the cells of the distal maxillary palp. Therefore, PB is required in cells outside the distal maxillary palp for the expression, by some mechanism, of a growth factor or factors that promote the growth of the distal maxillary palp...
2017: Genetics Research International
https://www.readbyqxmd.com/read/28351094/overexpression-of-lncrna-hotair-is-associated-with-poor-prognosis-in-thyroid-carcinoma-a-study-based-on-tcga-and-geo-data
#12
Hong-Mei Li, Hong Yang, Dong-Yue Wen, Yi-Huan Luo, Chun-Yan Liang, Deng-Hua Pan, Wei Ma, Gang Chen, Yun He, Jun-Qiang Chen
The role of long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) in thyroid carcinoma (TC) remains unclear. The current study was aimed to assess the clinical value of HOTAIR expression levels in TC based on publically available data and to evaluate its potential signaling pathways. The expression data of HOTAIR and clinical information concerning TC were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. Furthermore, 3 online biological databases, Starbase, Cbioportal, and Multi Experiment Matrix, were used to identify HOTAIR-related genes in TC...
March 28, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28344658/flightless-i-governs-cell-fate-by-recruiting-the-sumo-isopeptidase-senp3-to-distinct-hox-genes
#13
Arnab Nayak, Anja Reck, Christian Morsczeck, Stefan Müller
BACKGROUND: Despite recent studies on the role of ubiquitin-related SUMO modifier in cell fate decisions, our understanding on precise molecular mechanisms of these processes is limited. Previously, we established that the SUMO isopeptidase SENP3 regulates chromatin assembly of the MLL1/2 histone methyltransferase complex at distinct HOX genes, including the osteogenic master regulator DLX3. A comprehensive mechanism that regulates SENP3 transcriptional function was not understood. RESULTS: Here, we identified flightless-I homolog (FLII), a member of the gelsolin family of actin-remodeling proteins, as a novel regulator of SENP3...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28342055/the-analysis-of-lncrna-hotair-rs12826786-c-t-polymorphism-and-gastric-cancer-susceptibility-in-a-turkish-population-lack-of-any-association-in-a-hospital-based-case-control-study
#14
Y Ülger, E Dadaş, B Yalinbaş Kaya, A T Sümbül, A Genç, S Bayram
BACKGROUND: The HOX transcript antisense intergenic RNA (HOTAIR), a well-known long noncoding RNA (lncRNA), has been widely identified to participate in pathogenesis of multiple cancers. An aberrant up-regulation and biological functions have been observed in gastric cancer (GC). A common single nucleotide polymorphism (SNP) (rs12826786 C>T) at the HOTAIR has been reported to influence HOTAIR expression, but its association with GC has yet to be investigated in Turkish population. AIM: The aim of the present study was to investigate whether HOTAIR rs12826786 C>T polymorphism could be involved in the risk of GC susceptibility in Turkish population...
March 24, 2017: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/28337978/microrna-filters-hox-temporal-transcription-noise-to-confer-boundary-formation-in-the-spinal-cord
#15
Chung-Jung Li, Tian Hong, Ying-Tsen Tung, Ya-Ping Yen, Ho-Chiang Hsu, Ya-Lin Lu, Mien Chang, Qing Nie, Jun-An Chen
The initial rostrocaudal patterning of the neural tube leads to differential expression of Hox genes that contribute to the specification of motor neuron (MN) subtype identity. Although several 3' Hox mRNAs are expressed in progenitors in a noisy manner, these Hox proteins are not expressed in the progenitors and only become detectable in postmitotic MNs. MicroRNA biogenesis impairment leads to precocious expression and propagates the noise of Hoxa5 at the protein level, resulting in an imprecise Hoxa5-Hoxc8 boundary...
March 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28332497/epigenetically-driven-anatomical-diversity-of-synovial-fibroblasts-guides-joint-specific-fibroblast-functions
#16
Mojca Frank-Bertoncelj, Michelle Trenkmann, Kerstin Klein, Emmanuel Karouzakis, Hubert Rehrauer, Anna Bratus, Christoph Kolling, Maria Armaka, Andrew Filer, Beat A Michel, Renate E Gay, Christopher D Buckley, George Kollias, Steffen Gay, Caroline Ospelt
A number of human diseases, such as arthritis and atherosclerosis, include characteristic pathology in specific anatomical locations. Here we show transcriptomic differences in synovial fibroblasts from different joint locations and that HOX gene signatures reflect the joint-specific origins of mouse and human synovial fibroblasts and synovial tissues. Alongside DNA methylation and histone modifications, bromodomain and extra-terminal reader proteins regulate joint-specific HOX gene expression. Anatomical transcriptional diversity translates into joint-specific synovial fibroblast phenotypes with distinct adhesive, proliferative, chemotactic and matrix-degrading characteristics and differential responsiveness to TNF, creating a unique microenvironment in each joint...
March 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28293170/an-insight-into-the-increasing-role-of-lncrnas-in-the-pathogenesis-of-gliomas
#17
REVIEW
Yuanliang Yan, Zhijie Xu, Zhi Li, Lunquan Sun, Zhicheng Gong
Long non-coding RNAs (LncRNAs) are essential epigenetic regulators with critical roles in tumor initiation and malignant progression. However, the roles and mechanisms of aberrantly expressed lncRNAs in the pathogenesis of gliomas are not fully understood. With the development of deep sequencing analyses, an extensive amount of functional non-coding RNAs has been discovered in glioma tissues and cell lines. Additionally, the contributions of several lncRNAs, such as Hox transcript antisense intergenic RNA, H19 and Colorectal neoplasia differentially expressed, previously reported to be involved in other pathogenesis and processes to the oncogenesis of glioblastoma are currently addressed...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28283040/functional-variation-in-allelic-methylomes-underscores-a-strong-genetic-contribution-and-reveals-novel-epigenetic-alterations-in-the-human-epigenome
#18
Warren A Cheung, Xiaojian Shao, Andréanne Morin, Valérie Siroux, Tony Kwan, Bing Ge, Dylan Aïssi, Lu Chen, Louella Vasquez, Fiona Allum, Frédéric Guénard, Emmanuelle Bouzigon, Marie-Michelle Simon, Elodie Boulier, Adriana Redensek, Stephen Watt, Avik Datta, Laura Clarke, Paul Flicek, Daniel Mead, Dirk S Paul, Stephan Beck, Guillaume Bourque, Mark Lathrop, André Tchernof, Marie-Claude Vohl, Florence Demenais, Isabelle Pin, Kate Downes, Hendrick G Stunnenberg, Nicole Soranzo, Tomi Pastinen, Elin Grundberg
BACKGROUND: The functional impact of genetic variation has been extensively surveyed, revealing that genetic changes correlated to phenotypes lie mostly in non-coding genomic regions. Studies have linked allele-specific genetic changes to gene expression, DNA methylation, and histone marks but these investigations have only been carried out in a limited set of samples. RESULTS: We describe a large-scale coordinated study of allelic and non-allelic effects on DNA methylation, histone mark deposition, and gene expression, detecting the interrelations between epigenetic and functional features at unprecedented resolution...
March 10, 2017: Genome Biology
https://www.readbyqxmd.com/read/28257976/the-pbx1-lupus-susceptibility-gene-regulates-cd44-expression
#19
Yuxin Niu, Mayami Sengupta, Anton A Titov, Seung-Chul Choi, Laurence Morel
PBX1-d is novel splice isoform of pre-B-cell leukemia homeobox 1 (PBX1) that lacks its DNA-binding and Hox-binding domains, and functions as a dominant negative. We have shown that PBX1-d expression in CD4(+) T cells is associated with systemic lupus erythematosus (SLE) in a mouse model as well as in human subjects. More specifically, PBX1-d expression leads to the production of autoreactive activated CD4+ T cells, a reduced frequency and function of Foxp3+ regulatory T (Treg) cells and an expansion of follicular helper T (Tfh) cells...
May 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28251884/mir-101-3p-suppresses-hox-transcript-antisense-rna-hotair-induced-proliferation-and-invasion-through-directly-targeting-srf-in-gastric-carcinoma-cells
#20
Xiaoyu Wu, Jin Zhou, Zhenfeng Wu, Che Chen, Jiayun Liu, Guannan Wu, Jing Zhai, Fukun Liu, Gang Li
MiR-101-3p was identified as a tumor suppressor in several cancers, but its exact role in gastric adenocarcinoma is still largely unknown. In this study, we found that, compared with the RGM-1 human normal gastric epithelial cells, miR-101-3p was significantly downregulated in all the 6 human gastric adenocarcinoma cell lines, including BGC-823, MNK-45, MGC-803, SGC-7901, AGS and HGC-27. Overexpression miR-101-3p suppressed both the proliferation and invasion of AGS gastric adenocarcinoma cells and knockdown of miR-101-3p displayed an opposite effect...
March 2, 2017: Oncology Research
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