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https://www.readbyqxmd.com/read/28103614/enrichment-of-putative-pax8-target-genes-at-serous-epithelial-ovarian-cancer-susceptibility-loci
#1
Siddhartha P Kar, Emily Adler, Jonathan Tyrer, Dennis Hazelett, Hoda Anton-Culver, Elisa V Bandera, Matthias W Beckmann, Andrew Berchuck, Natalia Bogdanova, Louise Brinton, Ralf Butzow, Ian Campbell, Karen Carty, Jenny Chang-Claude, Linda S Cook, Daniel W Cramer, Julie M Cunningham, Agnieszka Dansonka-Mieszkowska, Jennifer Anne Doherty, Thilo Dörk, Matthias Dürst, Diana Eccles, Peter A Fasching, James Flanagan, Aleksandra Gentry-Maharaj, Rosalind Glasspool, Ellen L Goode, Marc T Goodman, Jacek Gronwald, Florian Heitz, Michelle A T Hildebrandt, Estrid Høgdall, Claus K Høgdall, David G Huntsman, Allan Jensen, Beth Y Karlan, Linda E Kelemen, Lambertus A Kiemeney, Susanne K Kjaer, Jolanta Kupryjanczyk, Diether Lambrechts, Douglas A Levine, Qiyuan Li, Jolanta Lissowska, Karen H Lu, Jan Lubiński, Leon F A G Massuger, Valerie McGuire, Iain McNeish, Usha Menon, Francesmary Modugno, Alvaro N Monteiro, Kirsten B Moysich, Roberta B Ness, Heli Nevanlinna, James Paul, Celeste L Pearce, Tanja Pejovic, Jennifer B Permuth, Catherine Phelan, Malcolm C Pike, Elizabeth M Poole, Susan J Ramus, Harvey A Risch, Mary Anne Rossing, Helga B Salvesen, Joellen M Schildkraut, Thomas A Sellers, Mark Sherman, Nadeem Siddiqui, Weiva Sieh, Honglin Song, Melissa Southey, Kathryn L Terry, Shelley S Tworoger, Christine Walsh, Nicolas Wentzensen, Alice S Whittemore, Anna H Wu, Hannah Yang, Wei Zheng, Argyrios Ziogas, Matthew L Freedman, Simon A Gayther, Paul D P Pharoah, Kate Lawrenson
BACKGROUND: Genome-wide association studies (GWAS) have identified 18 loci associated with serous ovarian cancer (SOC) susceptibility but the biological mechanisms driving these findings remain poorly characterised. Germline cancer risk loci may be enriched for target genes of transcription factors (TFs) critical to somatic tumorigenesis. METHODS: All 615 TF-target sets from the Molecular Signatures Database were evaluated using gene set enrichment analysis (GSEA) and three GWAS for SOC risk: discovery (2196 cases/4396 controls), replication (7035 cases/21 693 controls; independent from discovery), and combined (9627 cases/30 845 controls; including additional individuals)...
January 19, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28103578/prognostic-and-predictive-value-of-vhl-gene-alteration-in-renal-cell-carcinoma-a-meta-analysis-and-review
#2
Bum Jun Kim, Jung Han Kim, Hyeong Su Kim, Dae Young Zang
The von Hippel-Lindau (VHL) gene is often inactivated in sporadic renal cell carcinoma (RCC) by mutation or promoter hypermethylation. The prognostic or predictive value of VHL gene alteration is not well established. We conducted this meta-analysis to evaluate the association between the VHL alteration and clinical outcomes in patients with RCC. We searched PUBMED, MEDLINE and EMBASE for articles including following terms in their titles, abstracts, or keywords: 'kidney or renal', 'carcinoma or cancer or neoplasm or malignancy', 'von Hippel-Lindau or VHL', 'alteration or mutation or methylation', and 'prognostic or predictive'...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28103427/repeated-maximal-intensity-hypoxic-exercise-superimposed-to-hypoxic-residence-boosts-skeletal-muscle-transcriptional-responses-in-elite-team-sport-athletes
#3
Franck Brocherie, Grégoire P Millet, Gommaar D'Hulst, Ruud Van Thienen, Louise Deldicque, Olivier Girard
AIM: To determine whether repeated maximal-intensity hypoxic exercise induces larger beneficial adaptations on the hypoxia inducible factor-1α pathway and its target genes than similar normoxic exercise, when combined with chronic hypoxic exposure. METHODS: Lowland elite male team-sport athletes underwent 14 days of passive normobaric hypoxic exposure (≥14 h.day(-1) at Fi O2 14.5-14.2%) with the addition of six maximal-intensity exercise sessions either in normobaric hypoxia (Fi O2 ~14...
January 19, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28103290/involvement-of-ddah-adma-nos-cgmp-and-cox-2-ptgis-camp-pathways-in-human-tissue-kallikrein-1-protecting-erectile-function-in-aged-rats
#4
Kai Cui, Yang Luan, Zhe Tang, Ke Rao, Tao Wang, Zhong Chen, Shaogang Wang, Jihong Liu, Daowen Wang
Our previous studies had reported that Human Tissue Kallikrein 1 (hKLK1) preserved erectile function in aged transgenic rats, while the detailed mechanism of hKLK1 protecting erectile function in aged rats through activation of cGMP and cAMP was not mentioned. To explore the latent mechanism, male wild-type Sprague-Dawley rats (WTR) and transgenic rats harboring the hKLK1 gene (TGR) were fed to 4 and 18 months old and divided into four groups: young WTR (yWTR) as the control, aged WTR (aWTR), aged TGR (aTGR) and aged TGRs with HOE140 (aTGRH)...
2017: PloS One
https://www.readbyqxmd.com/read/28103286/mirnas-do-not-regulate-circadian-protein-synthesis-in-the-dinoflagellate-lingulodinium-polyedrum
#5
Steve Dagenais-Bellefeuille, Mathieu Beauchemin, David Morse
Dinoflagellates have been shown to express miRNA by bioinformatics and RNA blot (Northern) analyses. However, it is not yet known if miRNAs are able to alter gene expression in this class of organisms. We have assessed the possibility that miRNA may mediate circadian regulation of gene expression in the dinoflagellate Lingulodinium polyedrum using the Luciferin Binding Protein (LBP) as a specific example. LBP is a good candidate for regulation by miRNA since mRNA levels are constant over the daily cycle while protein synthesis is restricted by the circadian clock to a period of several hours at the start of the night phase...
2017: PloS One
https://www.readbyqxmd.com/read/28103282/two-novel-vesicle-inducing-proteins-in-plastids-1-genes-cloned-and-characterized-in-triticum-urartu
#6
Fei Gao, Bo Chen, Juan Jiao, Lijia Jia, Cuimin Liu
Vesicle-inducing protein in plastids 1 (Vipp1) is thought to play an important role both in thylakoid biogenesis and chloroplast envelope maintenance during stress. Vipp1 is conserved in photosynthetic organisms and forms a high homo-oligomer complex structure that may help sustain the membrane integrity of chloroplasts. This study cloned two novel VIPP1 genes from Triticum urartu and named them TuVipp1 and TuVipp2. Both proteins shared high identity with the homologous proteins AtVipp1 and CrVipp1. TuVipp1 and TuVipp2 were expressed in various organs of common wheat, and both genes were induced by light and various stress treatments...
2017: PloS One
https://www.readbyqxmd.com/read/28103279/aristaless-related-homeobox-arx-interacts-with-%C3%AE-catenin-bcl9-and-p300-to-regulate-canonical-wnt-signaling
#7
Il-Taeg Cho, Youngshin Lim, Jeffrey A Golden, Ginam Cho
Mutations in the Aristaless Related Homeobox (ARX) gene are associated with a spectrum of structural (lissencephaly) and functional (epilepsy and intellectual disabilities) neurodevelopmental disorders. How mutations in this single transcription factor can result in such a broad range of phenotypes remains poorly understood. We hypothesized that ARX functions through distinct interactions with specific transcription factors/cofactors to regulate unique target genes in different cell types. To identify ARX interacting proteins, we performed an unbiased proteomics screen and identified several components of the Wnt/β-catenin signaling pathway, including β-catenin (CTNNB1), B-cell CLL/lymphoma 9 (BCL9) and leucine rich repeat flightless interacting protein 2 (LRRFIP2), in cortical progenitor cells...
2017: PloS One
https://www.readbyqxmd.com/read/28103247/bombyx-mori-p-element-somatic-inhibitor-bmpsi-is-a-key-auxiliary-factor-for-silkworm-male-sex-determination
#8
Jun Xu, Shuqing Chen, Baosheng Zeng, Anthony A James, Anjiang Tan, Yongping Huang
Manipulation of sex determination pathways in insects provides the basis for a wide spectrum of strategies to benefit agriculture and public health. Furthermore, insects display a remarkable diversity in the genetic pathways that lead to sex differentiation. The silkworm, Bombyx mori, has been cultivated by humans as a beneficial insect for over two millennia, and more recently as a model system for studying lepidopteran genetics and development. Previous studies have identified the B. mori Fem piRNA as the primary female determining factor and BmMasc as its downstream target, while the genetic scenario for male sex determination was still unclear...
January 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28103241/contextual-refinement-of-regulatory-targets-reveals-effects-on-breast-cancer-prognosis-of-the-regulome
#9
Erik Andrews, Yue Wang, Tian Xia, Wenqing Cheng, Chao Cheng
Gene expression regulators, such as transcription factors (TFs) and microRNAs (miRNAs), have varying regulatory targets based on the tissue and physiological state (context) within which they are expressed. While the emergence of regulator-characterizing experiments has inferred the target genes of many regulators across many contexts, methods for transferring regulator target genes across contexts are lacking. Further, regulator target gene lists frequently are not curated or have permissive inclusion criteria, impairing their use...
January 19, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28103240/rfx2-stabilizes-foxj1-binding-at-chromatin-loops-to-enable-multiciliated-cell-gene-expression
#10
Ian K Quigley, Chris Kintner
Cooperative transcription factor binding at cis-regulatory sites in the genome drives robust eukaryotic gene expression, and many such sites must be coordinated to produce coherent transcriptional programs. The transcriptional program leading to motile cilia formation requires members of the DNA-binding forkhead (Fox) and Rfx transcription factor families and these factors co-localize to cilia gene promoters, but it is not clear how many cilia genes are regulated by these two factors, whether these factors act directly or indirectly, or how these factors act with specificity in the context of a 3-dimensional genome...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28103160/yersinia-pestis-acetyltransferase-mediated-dual-acetylation-at-the-serine-and-lysine-residues-enhances-the-auto-ubiquitination-of-ubiquitin-ligase-march8-in-human-cells
#11
Cuiling Li, Daoguang Wang, Xin Lv, Ruirui Jing, Baibin Bi, Xinjun Chen, Jisheng Guo, Fengqin Wang, Shengnan Sun, Kazem M Azadzoi, Jing-Hua Yang
Lysine acetylation is known as a post translational modification (PTM) by histone acetyltransferases (HAT) that modifies histones and non-histone proteins to regulate gene expression. Serine acetylation, however, is reported in mammalian hosts by serine acetyltransferase of Yersinia pestis (YopJ) during infection. The protein target and cellular function of bacterial YopJ in mammalian systems are not fully addressed. Here we report dual acetylation at the serine and lysine residues by transiently expressed serine acetyltransferase YopJ mimicking Y...
January 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28102867/a-systems-approach-for-the-elucidation-of-crucial-genes-and-network-constituents-of-cervical-intraepithelial-neoplasia-1-cin1
#12
Shikha Suman, Ashutosh Mishra, Anurag Kulshrestha
Cervical intra-epithelial neoplasia 1 (CIN1) is a pre-cancerous cervical cancer condition characterized by changes in the squamous cells of the cervix. Early detection may facilitate treatment as CIN1 may increase the risk of developing cervical cancer. An extensive system level analysis has been carried out to detect crucial network components of CIN1. Differential expression analysis was performed to identify genes that are differentially expressed in CIN1 in comparison to normal cells. Gene Ontology (GO) and pathway enrichment analyses of DEGs were followed by the construction of a protein-protein interaction (PPI) network...
January 19, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28102866/the-dna-target-determines-the-dimerization-partner-selected-by-bhlhz-like-hybrid-proteins-ahrjun-and-arntfos
#13
Ichiro Inamoto, Gang Chen, Jumi A Shin
The molecular basis of protein-partner selection and DNA binding of the basic helix-loop-helix (bHLH) and basic region-leucine zipper (bZIP) superfamilies of dimeric transcription factors is fundamental toward understanding gene regulation. Because these families share structural similarities, we swapped the bHLH and leucine zipper (LZ) modules between families to uncover how individual modules influence protein-partnering and protein:DNA complexation. We previously described ArntFos, a bHLHZ-like hybrid of the bHLH domain from the bHLH/PAS protein Arnt and LZ from the bZIP protein c-Fos, binding to the Arnt E-box site (TCACGTGA) as a homodimer...
January 19, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28102861/clinical-utility-of-next-generation-sequencing-for-inherited-bone-marrow-failure-syndromes
#14
Hideki Muramatsu, Yusuke Okuno, Kenichi Yoshida, Yuichi Shiraishi, Sayoko Doisaki, Atsushi Narita, Hirotoshi Sakaguchi, Nozomu Kawashima, Xinan Wang, Yinyan Xu, Kenichi Chiba, Hiroko Tanaka, Asahito Hama, Masashi Sanada, Yoshiyuki Takahashi, Hitoshi Kanno, Hiroki Yamaguchi, Shouichi Ohga, Atsushi Manabe, Hideo Harigae, Shinji Kunishima, Eiichi Ishii, Masao Kobayashi, Kenichi Koike, Kenichiro Watanabe, Etsuro Ito, Minoru Takata, Miharu Yabe, Seishi Ogawa, Satoru Miyano, Seiji Kojima
PURPOSE: Precise genetic diagnosis of inherited bone marrow failure syndromes (IBMFS), a heterogeneous group of genetic disorders, is challenging but essential for precise clinical decision making. METHODS: We analyzed 121 IBMFS patients using a targeted sequencing covering 184 associated genes and 250 IBMFS patients using whole-exome sequencing (WES). RESULTS: We achieved successful genetic diagnoses for 53 of 121 patients (44%) using targeted sequencing and for 68 of 250 patients (27%) using WES...
January 19, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28102847/curcumin-represses-mouse-3t3-l1-cell-adipogenic-differentiation-via-inhibiting-mir-17-5p-and-stimulating-the-wnt-signalling-pathway-effector-tcf7l2
#15
Lili Tian, Zhuolun Song, Weijuan Shao, William W Du, Lisa R Zhao, Kejing Zeng, Burton B Yang, Tianru Jin
Understanding mechanisms underlying adipogenic differentiation may lead to the discovery of novel therapeutic targets for obesity. Wnt signalling pathway activation leads to repressed adipogenic differentiation while certain microRNAs may regulate pre-adipocyte proliferation and differentiation. We show here that in mouse white adipose tissue, miR-17-5p level is elevated after high fat diet consumption. miR-17-5p upregulates adipogenic differentiation, as its over-expression increased while its inhibition repressed 3T3-L1 differentiation...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102846/hepatitis-b-virus-x-protein-promotes-the-stem-like-properties-of-ov6-cancer-cells-in-hepatocellular-carcinoma
#16
Chao Wang, Ming-da Wang, Peng Cheng, Hai Huang, Wei Dong, Wei-Wei Zhang, Peng-Peng Li, Chuan Lin, Ze-Ya Pan, Meng-Chao Wu, Wei-Ping Zhou
Hepatitis B virus X protein (HBx) and cancer stem-like cells (CSCs) have both been implicated in the occurrence and development of HBV-related hepatocellular carcinoma (HCC). However, whether HBx contributes to the stem-like properties of OV6(+) CSCs in HCC remains elusive. In this study, we showed that the concomitant expression of HBx and OV6 was closely associated with the clinical outcomes and prognosis of patients with HBV-related HCC. HBx was required for the stem-like properties of OV6(+) liver CSCs, including self-renewal, stem cell-associated gene expression, tumorigenicity and chemoresistance...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102845/h19-let-7-lin28-reciprocal-negative-regulatory-circuit-promotes-breast-cancer-stem-cell-maintenance
#17
Fei Peng, Ting-Ting Li, Kai-Li Wang, Guo-Qing Xiao, Ju-Hong Wang, Hai-Dong Zhao, Zhi-Jie Kang, Wen-Jun Fan, Li-Li Zhu, Mei Li, Bai Cui, Fei-Meng Zheng, Hong-Jiang Wang, Eric W-F Lam, Bo Wang, Jie Xu, Quentin Liu
Long noncoding RNA-H19 (H19), an imprinted oncofetal gene, has a central role in carcinogenesis. Hitherto, the mechanism by which H19 regulates cancer stem cells, remains elusive. Here we show that breast cancer stem cells (BCSCs) express high levels of H19, and ectopic overexpression of H19 significantly promotes breast cancer cell clonogenicity, migration and mammosphere-forming ability. Conversely, silencing of H19 represses these BCSC properties. In concordance, knockdown of H19 markedly inhibits tumor growth and suppresses tumorigenesis in nude mice...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102838/autophagy-dysregulation-in-danon-disease
#18
Anna Chiara Nascimbeni, Marina Fanin, Corrado Angelini, Marco Sandri
The autophagy-lysosome system is critical for muscle homeostasis and defects in lysosomal function result in a number of inherited muscle diseases, generally referred to as autophagic vacuolar myopathies (AVMs). Among them, Danon Disease (DD) and glycogen storage disease type II (GSDII) are due to primary lysosomal protein defects. DD is characterized by mutations in the lysosome-associated membrane protein 2 (LAMP2) gene. The DD mouse model suggests that inefficient lysosome biogenesis/maturation and impairment of autophagosome-lysosome fusion contribute to the pathogenesis of muscle wasting...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102700/aryl-hydrocarbon-receptor-deficient-mice-are-protected-from-high-fat-diet-induced-changes-in-metabolic-rhythms
#19
Cassie Jaeger, Canxin Xu, Mingwei Sun, Stacey Krager, Shelley A Tischkau
High fat diet (HFD) consumption alters the synchronized circadian timing system resulting in harmful loss, gain or shift of transcriptional oscillations. The aryl hydrocarbon receptor (AhR) shares structural homology to clock genes, containing both PAS domains and basic helix-loop helix structural motifs, allowing for interaction with components of the primary circadian feedback loop. Activation of AhR alters circadian rhythmicity, primarily through inhibition of Clock/Bmal1-mediated regulation of Per1. AhR-deficient mice are protected from diet-induced metabolic dysfunction, exhibiting enhanced insulin sensitivity and glucose tolerance...
January 19, 2017: Chronobiology International
https://www.readbyqxmd.com/read/28102564/pkn2-is-essential-for-mouse-embryonic-development-and-proliferation-of-mouse-fibroblasts
#20
Sally Danno, Koji Kubouchi, Mona Mehruba, Manabu Abe, Rie Natsume, Kenji Sakimura, Satoshi Eguchi, Masahiro Oka, Masanori Hirashima, Hiroki Yasuda, Hideyuki Mukai
PKN2, a member of the protein kinase N (PKN) family, has been suggested by in vitro culture cell experiments to bind to Rho/Rac GTPases and contributes to cell-cell contact and cell migration. To unravel the in vivo physiological function of PKN2, we targeted the PKN2 gene. Constitutive disruption of the mouse PKN2 gene resulted in growth retardation and lethality before embryonic day (E) 10.5. PKN2(-/-) embryo did not undergo axial turning and showed insufficient closure of the neural tube. Mouse embryonic fibroblasts (MEFs) derived from PKN2(-/-) embryos at E9...
January 19, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
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