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https://www.readbyqxmd.com/read/28231541/endogenous-microrna-424-predicts-clinical-outcome-and-its-inhibition-acts-as-cancer-suppressor-in-human-non-small-cell-lung-cancer
#1
Yu Wang, Zhenyang Lv, Junfeng Fu, Ze Wang, Zhe Fan, Ting Lei
PURPOSE: We examined the expression, clinical correlation and functional mechanisms of endogenous microRNA-424 (miR-424) in human non-small cell lung cancer (NSCLC). METHODS: Expression pattern of endogenous miR-424 was examined by qRT-PCR in clinical samples obtained from 233 NSCLC patients. Correlations between differential miR-424 expression level (low vs. high) and NSCLC patients' clinicopathological parameters or survival were statistically examined. In in vitro NSCLC H596 and SW900 cells, miR-424 was either upregulated or downregulation by lentiviral transduction...
February 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28229964/csfv-proliferation-is-associated-with-gbf1-and-rab2
#2
Wulong Liang, Minping Zheng, Changlei Bao, Yanming Zhang
The Golgi apparatus and its resident proteins are utilized and regulated by viruses to facilitate their proliferation. In this study, we investigated Classical swine fever virus (CSFV) proliferation when the function of the Golgi was disturbed. Golgi function was disturbed using chemical inhibitors, namely, brefeldin A (BFA) and golgicide A (GCA), and RNA interfering targets, such as the Golgi-specific BFA-resistance guanine nucleotide exchange factor 1 (GBF1) and Rab2 GTPases. CSFV proliferation was significantly inhibited during RNA replication and viral particle generation after BFA and GCA treatment...
March 2017: Journal of Biosciences
https://www.readbyqxmd.com/read/28229507/a-samhd1-mutation-associated-with-aicardi-gouti%C3%A3-res-syndrome-uncouples-the-ability-of-samhd1-to-restrict-hiv-1-from-its-ability-to-downmodulate-type-i-interferon-in-humans
#3
Tommy E White, Alberto Brandariz-Nuñez, Alicia Martinez-Lopez, Caitlin Knowlton, Gina Lenzi, Baek Kim, Dmitri Ivanov, Felipe Diaz-Griffero
Mutations in the human SAMHD1 gene are known to correlate with the development of the Aicardi-Goutières Syndrome (AGS), which is an inflammatory encephalopathy that exhibits neurological dysfunction characterized by increased production of type I interferon (IFN); this evidence has lead to the concept that the SAMHD1 protein negatively regulates the type I IFN response. Additionally, the SAMHD1 protein has been shown to prevent efficient HIV-1 infection of macrophages, dendritic cells and resting CD4+ T cells...
February 22, 2017: Human Mutation
https://www.readbyqxmd.com/read/28228523/vpx-overcomes-a-samhd1-independent-block-to-hiv-reverse-transcription-that-is-specific-to-resting-cd4-t-cells
#4
Hanna-Mari Baldauf, Lena Stegmann, Sarah-Marie Schwarz, Ina Ambiel, Maud Trotard, Margarethe Martin, Manja Burggraf, Gina M Lenzi, Helena Lejk, Xiaoyu Pan, Oliver I Fregoso, Efrem S Lim, Libin Abraham, Laura A Nguyen, Frank Rutsch, Renate König, Baek Kim, Michael Emerman, Oliver T Fackler, Oliver T Keppler
Early after entry into monocytes, macrophages, dendritic cells, and resting CD4 T cells, HIV encounters a block, limiting reverse transcription (RT) of the incoming viral RNA genome. In this context, dNTP triphosphohydrolase SAM domain and HD domain-containing protein 1 (SAMHD1) has been identified as a restriction factor, lowering the concentration of dNTP substrates to limit RT. The accessory lentiviral protein X (Vpx) proteins from the major simian immunodeficiency virus of rhesus macaque, sooty mangabey, and HIV-2 (SIVsmm/SIVmac/HIV-2) lineage packaged into virions target SAMHD1 for proteasomal degradation, increase intracellular dNTP pools, and facilitate HIV cDNA synthesis...
February 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28225770/a-distal-intergenic-region-controls-pancreatic-endocrine-differentiation-by-acting-as-a-transcriptional-enhancer-and-as-a-polycomb-response-element
#5
Joris van Arensbergen, Sebastien Dussaud, Corinne Pardanaud-Glavieux, Javier García-Hurtado, Claire Sauty, Aline Guerci, Jorge Ferrer, Philippe Ravassard
Lineage-selective expression of developmental genes is dependent on the interplay between activating and repressive mechanisms. Gene activation is dependent on cell-specific transcription factors that recognize transcriptional enhancer sequences. Gene repression often depends on the recruitment of Polycomb group (PcG) proteins, although the sequences that underlie the recruitment of PcG proteins, also known as Polycomb response elements (PREs), remain poorly understood in vertebrates. While distal PREs have been identified in mammals, a role for positive-acting enhancers in PcG-mediated repression has not been described...
2017: PloS One
https://www.readbyqxmd.com/read/28223821/asparaginyl-endopeptidase-improves-the-resistance-of-microtubule-targeting-drugs-in-gastric-cancer-through-iqgap1-modulating-the-egfr-jnk-erk-signaling-pathway
#6
Yuehong Cui, Qian Li, Hong Li, Yan Wang, Hongshan Wang, Weidong Chen, Shangmin Zhang, Jian Cao, Tianshu Liu
PURPOSE: In recent years, understanding of the role of asparaginyl endopeptidase (AEP) in tumorigenesis has steadily increased. In this study, we investigated whether AEP expression correlates with sensitivity to chemotherapeutic drugs in gastric cancer and explored the mechanism. PATIENTS AND METHODS: AEP expression in the serum of patients' peripheral blood was measured by enzyme-linked immunosorbent assay. Patient survival time was evaluated using univariate and multivariate analyses...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28223039/oncogene-lsd1-is-epigenetically-suppressed-by-mir-137-overexpression-in-human-non-small-cell-lung-cancer
#7
Xin Zhang, Xiujuan Zhang, Bo Yu, Rongpeng Hu, Lanxiang Hao
PURPOSE: We examined the epigenetic regulation of microRNA-137 (miR-137) on lysine-specific demethylase 1 (KDM1A, or LSD1) induced oncogenic effects in NSCLC. METHODS: NSCLC cell lines, A549 and H460 cells were transfected with a mammalian LSD1 overexpression plasmid. It's effects on endogenous KDM1A gene and LSD1 protein expressions were examined by qRT-PCR and western blot assays. NSCLC proliferation and migration were also examined by MTT proliferation and wound-scratch assays, respectively...
February 18, 2017: Biochimie
https://www.readbyqxmd.com/read/28222938/the-role-of-mir-17-92-cluster-in-the-expression-of-tumor-suppressor-genes-in-unrestricted-somatic-stem-cells
#8
Rezvan Tavakoli, Saeid Vakilian, Lida Langroudi, Ehsan Arefian, Mehdi Sahmani, Masoud Soleimani, Fatemeh Jamshidi-Adegani
The miR-17-92 cluster consisted of seven miRNAs (mir-17-5p, -17-3p, -18a, -19a, -20a, -19b-1, and -92a-1). Previous studies have shown this cluster has been over-expressed in several cancers. The aim of this study was to evaluate the over-expression impacts of miR-17-92 on stem cells. In the current work, the effect of miR-17-92 cluster which was cloned in Lentiviral vector has been investigated on unrestricted somatic stem cells (USSCs). Tumor suppressor genes (p53, p15, RBL1, SMAD2, SMAD4, and MAPK-1) expression, especially p53, was considerably reduced...
February 17, 2017: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/28220627/downregulation-of-mirna-141-in-breast-cancer-cells-is-associated-with-cell-migration-and-invasion-involvement-of-anp32e-targeting
#9
Ping Li, Tao Xu, Xin Zhou, Liangying Liao, Guolian Pang, Wan Luo, Lu Han, Jiankun Zhang, Xianyong Luo, Xiaobing Xie, Kuichun Zhu
MicroRNAs (miRNAs) regulate many cellular activities, including cancer development, progression, and metastasis. Some miRNAs are involved in breast cancer (BC) migration and invasion, thus affect patients' prognosis. Microarray analysis was performed to compare miRNA expression in BC tissues, and results confirmed by qPCR. BC cell migration and invasion were studied in vitro with MDA-MB-231 cells using microplate transwell assays. miRNA targeting was investigated using luciferase assays, qPCR, and Western blot analysis in cells with overexpression of miRNA mimics...
February 21, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28214829/ephb4-regulates-self-renewal-proliferation-and-neuronal-differentiation-of-human-embryonic-neural-stem-cells-in-vitro
#10
Tingting Liu, Xianwei Zeng, Fangling Sun, Hongli Hou, Yunqian Guan, Deyu Guo, Houxi Ai, Wen Wang, Guojun Zhang
BACKGROUND/AIMS: EphB4 belongs to the largest family of Eph receptor tyrosine kinases. It contributes to a variety of pathological progresses of cancer malignancy. However, little is known about its role in neural stem cells (NSCs). This study examined whether EphB4 is required for proliferation and differentiation of human embryonic neural stem cells (hNSCs) in vitro. METHODS: We up- and down-regulated EphB4 expression in hNSCs using lentiviral over-expression and shRNA knockdown constructs and then investigated the influence of EphB4 on the properties of hNSCs...
February 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28213976/enhancement-of-%C3%AE-globin-gene-expression-in-thalassemic-ivs2-654-induced-pluripotent-stem-cell-derived-erythroid-cells-by-modified-u7-snrna
#11
Phetcharat Phanthong, Suparerk Borwornpinyo, Narisorn Kitiyanant, Natee Jearawiriyapaisarn, Lalana Nuntakarn, Jirawat Saetan, Tiwaporn Nualkaew, Khanit Sa-Ngiamsuntorn, Usanarat Anurathapan, Andras Dinnyes, Yindee Kitiyanant, Suradej Hongeng
The therapeutic use of patient-specific induced pluripotent stem cells (iPSCs) is emerging as a potential treatment of β-thalassemia. Ideally, patient-specific iPSCs would be genetically corrected by various approaches to treat β-thalassemia including lentiviral gene transfer, lentivirus-delivered shRNA, and gene editing. These corrected iPSCs would be subsequently differentiated into hematopoietic stem cells and transplanted back into the same patient. In this article, we present a proof of principle study for disease modeling and screening using iPSCs to test the potential use of the modified U7 small nuclear (sn) RNA to correct a splice defect in IVS2-654 β-thalassemia...
February 18, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28209530/slc39a6-promotes-aggressiveness-of-esophageal-carcinoma-cells-by-increasing-intracellular-levels-of-zinc-activating-phosphatidylinositol-3-kinase-signaling-and-upregulating-genes-that-regulate-metastasis
#12
Xinxin Cheng, Lixuan Wei, Xudong Huang, Jian Zheng, Mingming Shao, Ting Feng, Jun Li, Yaling Han, Wenle Tan, Wen Tan, Dongxin Lin, Chen Wu
BACKGROUND & AIMS: A common variant in the solute carrier family 39 member 6 gene (SLC39A6) has been associated with survival times of patients with esophageal squamous-cell carcinoma (ESCC). We investigated the function of SLC39A6 and ways in which this variant affects tumor progression by studying ESCC samples and cell lines. METHODS: SLC39A6 was expressed, or knocked down by expression of small hairpin RNAs, in ESCC cells (KYSE30 and KYSE450) and HeLa cells using lentiviral vectors; we analyzed effects on proliferation, colony formation, migration, and invasion in vitro...
February 13, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28205094/knockdown-of-cardiac-kir3-1-gene-with-sirna-can-improve-bradycardia-in-an-experimental-sinus-bradycardia-rat-model
#13
Yang Li, Xiaodan Fu, Zhi Zhang, Bo Yu
The objective of this study was to explore whether the inhibition of potassium inwardly rectifying channel (Kir3.1) with short interfering RNA (siRNA) can improve bradycardia in an experimental sinus bradycardia rat model. 54 Sprague Dawley (SD) rats were randomly divided into three groups: experimental group, control group, and sham group. Sinus bradycardia model was established in SD rats through chemical ablation of sinoatrial (SA) node with 20% formaldehyde. Variations of Kir3.1 expression at mRNA and protein level were examined with qPCR and Western blotting...
February 15, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28202763/inhibition-of-vpx-mediated-samhd1-and-vpr-mediated-hltf-degradation-by-selective-disruption-of-viral-crl4-dcaf1-e3-ubiquitin-ligase-assembly
#14
Hong Wang, Haoran Guo, Jiaming Su, Yajuan Rui, Wenwen Zheng, Wenying Gao, Wenyan Zhang, Zhaolong Li, Guanchen Liu, Wei Wei, Xiao-Fang Yu
The lentiviral accessory proteins Vpx and Vpr are known to utilize CRL4 (DCAF1) E3 ligase to induce the degradation of the host restriction factor SAMHD1 or transcriptional factor HLTF, respectively. Selective disruption of viral CRL4 (DCAF1) E3 ligase could be a promising antiviral strategy. Recently, we have determined that post-translational modification (neddylation) of Cullin-4 is required for the activation of Vpx-CRL4 (DCAF1) E3 ligase. However, the mechanism of Vpx/Vpr-CRL4 (DCAF1) E3 ligase assembly is still poorly understood...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28202390/systemic-injection-of-rpe65-programmed-bone-marrow-derived-cells-prevents-progression-of-chronic-retinal-degeneration
#15
Xiaoping Qi, S Louise Pay, Yuanqing Yan, James Thomas, Alfred S Lewin, Lung-Ji Chang, Maria B Grant, Michael E Boulton
Bone marrow stem and progenitor cells can differentiate into a range of non-hematopoietic cell types, including retinal pigment epithelium (RPE)-like cells. In this study, we programmed bone marrow-derived cells (BMDCs) ex vivo by inserting a stable RPE65 transgene using a lentiviral vector. We tested the efficacy of systemically administered RPE65-programmed BMDCs to prevent visual loss in the superoxide dismutase 2 knockdown (Sod2 KD) mouse model of age-related macular degeneration. Here, we present evidence that these RPE65-programmed BMDCs are recruited to the subretinal space, where they repopulate the RPE layer, preserve the photoreceptor layer, retain the thickness of the neural retina, reduce lipofuscin granule formation, and suppress microgliosis...
February 12, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28199986/a-tree-shrew-glioblastoma-model-recapitulates-features-of-human-glioblastoma
#16
Yaohui Tong, Junjun Hao, Qiu Tu, Hualin Yu, Lanzhen Yan, Yuan Li, Longbao Lv, Fei Wang, Antonio Iavarone, Xudong Zhao
Tupaia belangeri (tree shrew), an animal species whose genome has significantly higher similarity to primates than rodents, has been used in biomedical research. To generate animal models that reproduce the human tumors more faithfully than rodents, we present the first report of a cancer model mimicking human tumor genetics in tree shrew. By engineering a lentiviral system for the transduction of mutant H-Ras and a shRNA against tree shrew p53, we successfully generated malignant glioma in tree shrew. The tree shrew glioma exhibited aggressive behavior and a relatively short latency, and markedly reduced animal survival...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28199983/a-versatile-system-for-rapid-multiplex-genome-edited-car-t-cell-generation
#17
Jiangtao Ren, Xuhua Zhang, Xiaojun Liu, Chongyun Fang, Shuguang Jiang, Carl H June, Yangbing Zhao
The therapeutic potential of CRISPR system has already been demonstrated in many instances and begun to overlap with the rapidly expanding field of cancer immunotherapy, especially on the production of genetically modified T cell receptor or chimeric antigen receptor (CAR) T cells. Efficient genomic disruption of multiple gene loci to generate universal donor cells, as well as potent effector T cells resistant to multiple inhibitory pathways such as PD-1 and CTLA4 is an attractive strategy for cell therapy...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28197078/redundant-postsynaptic-functions-of-syncams-1-3-during-synapse-formation
#18
Daniel K Fowler, James H Peters, Carly Williams, Philip Washbourne
Investigating the roles of synaptogenic adhesion molecules during synapse formation has proven challenging, often due to compensatory functions between additional family members. The synaptic cell adhesion molecules 1-3 (SynCAM1-3) are expressed both pre- and postsynaptically, share highly homologous domains and are synaptogenic when ectopically presented to neurons; yet their endogenous functions during synaptogenesis are unclear. Here we report that SynCAM1-3 are functionally redundant and collectively necessary for synapse formation in cultured hippocampal neurons...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28196906/a-high-throughput-image-based-screen-to-identify-kinases-involved-in-brown-adipocyte-development
#19
Aliki Perdikari, Elisabeth Kulenkampff, Carla Rudigier, Heike Neubauer, Gerd Luippold, Norbert Redemann, Christian Wolfrum
Brown adipose tissue (BAT) is responsible for thermogenesis that is not associated with shivering through the process of converting chemical energy into heat through uncoupling protein 1 (UCP1) in the mitochondria. Thus, expanding or activating BAT could be a potential tool against obesity. To analyze the effect of kinase signaling on brown adipocyte formation, a process that describes the acquisition of the ability to dissipate energy as heat, we performed lentiviral-mediated short hairpin knockdown or used pharmacological inhibitors in a high-content and high-throughput in vitro image-based screen...
February 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28193696/astrocytic-orosomucoid-2-modulates-microglial-activation-and-neuroinflammation
#20
Myungjin Jo, Jong-Heon Kim, Gyunjee Song, Minchul Seo, Eun Mi Hwang, Kyoungho Suk
Orosomucoid (ORM) is an acute-phase protein that belongs to the immunocalin subfamily, a group of small-molecule binding proteins with immunomodulatory functions. Little is known about the role of ORM proteins in the central nervous system. The aim of the present study was to investigate the brain expression of ORM and its role in neuroinflammation. Expression of Orm2, but not Orm1 or Orm3, was highly induced in the mouse brain after systemic injection of lipopolysaccharide (LPS). Plasma levels of ORM2 were also significantly higher in patients with cognitive impairment than in normal subjects...
February 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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