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Alexandra Sufit, Alisa B Lee-Sherick, Deborah DeRyckere, Manali Rupji, Bhakti Dwivedi, Marileila Varella-Garcia, Angela M Pierce, Jeanne Kowalski, Xiaodong Wang, Stephen V Frye, H Shelton Earp, Amy K Keating, Douglas K Graham
BACKGROUND: MER receptor tyrosine kinase (MERTK) is expressed in a variety of malignancies, including glioblastoma multiforme (GBM). Our previous work demonstrated that inhibition of MERTK using RNA interference induced cell death and chemosensitivity in GBM cells, implicating MERTK as a potential therapeutic target. Here we investigate whether a novel MERTK-selective small molecule tyrosine kinase inhibitor, UNC2025, has similar anti-tumor effects in GBM cell lines. METHODS: Correlations between expression of GAS6, a MERTK ligand, and prognosis were determined using data from the TCGA database...
2016: PloS One
Yong Huang, Jinxiu Huang, Renli Qi, Qi Wang, Yongjiang Wu, Jing Wang
MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate growth, development, and programmed death of cells. A newly-published study has shown that miRNA-23a could regulate 3T3-L1 adipocyte differentiation. Here, we identified miRNA-23a as a negative regulator of 3T3-L1 adipocyte differentiation again. Over-expression of miRNA-23a inhibited differentiation and decreased lipogenesis as well as down-regulated mRNA and protein expression of both peroxisome proliferator-activated receptor (PPAR) γ and fatty acid binding protein (FABP) 4, whereas knock down of miRNA-23a showed the opposite effects on differentiation as well as increasing the number of apoptotic cells...
October 24, 2016: Genes
Alicja Pacholewska, Núria Mach, Xavier Mata, Anne Vaiman, Laurent Schibler, Eric Barrey, Vincent Gerber
BACKGROUND: MiRNAs regulate multiple genes at the post-transcriptional level and therefore play an important role in many biological processes. It has been suggested that miRNA exported outside the cells contribute to inter-cellular communication. Consequently, circulating miRNAs are of particular interest and are promising biomarkers for many diseases. The number of miRNAs annotated in the horse genome is much lower compared to model organisms like human and mouse. We therefore aimed to identify novel equine miRNAs for tissue types and breed in serum...
October 26, 2016: BMC Genomics
Wim Trypsteen, Pejman Mohammadi, Clarissa Van Hecke, Pieter Mestdagh, Steve Lefever, Yvan Saeys, Pieter De Bleser, Jo Vandesompele, Angela Ciuffi, Linos Vandekerckhove, Ward De Spiegelaere
Studying the effects of HIV infection on the host transcriptome has typically focused on protein-coding genes. However, recent advances in the field of RNA sequencing revealed that long non-coding RNAs (lncRNAs) add an extensive additional layer to the cell's molecular network. Here, we performed transcriptome profiling throughout a primary HIV infection in vitro to investigate lncRNA expression at the different HIV replication cycle processes (reverse transcription, integration and particle production). Subsequently, guilt-by-association, transcription factor and co-expression analysis were performed to infer biological roles for the lncRNAs identified in the HIV-host interplay...
October 26, 2016: Scientific Reports
Ehsan Malek, Byung-Gyu Kim, James J Driscoll
While the clinical benefit of proteasome inhibitors (PIs) for multiple myeloma (MM) treatment remains unchallenged, dose-limiting toxicities and the inevitable emergence of drug resistance limit their long-term utility. Disease eradication is compromised by drug resistance that is either present de novo or therapy-induced, which accounts for the majority of tumor relapses and MM-related deaths. Non-coding RNAs (ncRNAs) are a broad class of RNA molecules, including long non-coding RNAs (lncRNAs), that do not encode proteins but play a major role in regulating the fundamental cellular processes that control cancer initiation, metastasis, and therapeutic resistance...
October 6, 2016: Genes
N Wu, U Gaur, Q Zhu, B Chen, Z Xu, X Zhao, M Yang, D Li
MicroRNA (miRNA) is a highly conserved class of small noncoding RNA about 19-24 nucleotides in length that function in a specific manner to post-transcriptionally regulate gene expression in organisms. Tissue miRNA expression studies have discovered a myriad of functions for miRNAs in various aspects, but a role for miRNAs in chicken ovarian tissue at 300 days of age has not hitherto been reported. In this study, we performed the first miRNA analysis of ovarian tissues in chickens with low and high rates of egg production using high-throughput sequencing...
October 26, 2016: Animal Genetics
Leila Maghen, Ekaterina Shlush, Itai Gat, Melissa Filice, Tanya Barretto, Keith Jarvi, Kirk Lo, Andree S Gauthier-Fisher, Clifford L Librach
The expansion of functional testicular biopsy-derived human spermatogonial stem cells (hSSC) ex-vivo may enable the restoration of fertility in pre-pubertal males having undergone gonadotoxic therapies or men with severe male factor infertility. Various somatic cells are known to regulate SSC homeostasis and spermatogenesis in the developing and adult testis. Prior attempts to recapitulate this niche demonstrated the requirement of feeder cells, such as endogenous testicular somatic cells, for germ cell expansion ex-vivo...
October 25, 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
Yohsuke Yagi, Takuya Ohkubo, Hideya Kawaji, Akira Machida, Haruka Miyata, Saori Goda, Sugata Roy, Yoshihide Hayashizaki, Harukazu Suzuki, Takanori Yokota
MicroRNAs (miRNAs), particularly those found in human body fluids, have been suggested as potential biomarkers. Among various body fluids, the cerebrospinal fluid (CSF) shows promise as a profiling target for diagnosis and monitoring of neurological diseases. However, relevant genome-scale studies are limited and no studies have profiled exosomal miRNAs in CSF. Therefore, we conducted a next-generation sequencing-based genome-wide survey of small RNAs in the exosomal and non-exosomal (supernatant) fractions of healthy human CSF as well as serum in each donor...
October 22, 2016: Neuroscience Letters
Cuncun Chen, Min Wu, Wen Zhang, Wei Lu, Min Zhang, Zhanqing Zhang, Xiaonan Zhang, Zhenghong Yuan
Multi-layered mechanisms of virus host interaction exist for chronic hepatitis B virus (HBV) infection, which have been typically manifested at the microRNA level. Our previous study suggested that miRNA-939 (miR-939) may play a potential role in regulating HBV replication. Here we further investigated the mechanism by which miR-939 regulates HBV life cycle. We found that miR-939 inhibited the abundance of viral RNAs without direct miRNA-mRNA base pairing, but via host factors. Expression profiling and functional validation identified Jmjd3 as a target responsible for miR-939 induced anti-HBV effect...
October 25, 2016: Scientific Reports
Donna M Bond, Nick W Albert, Robyn H Lee, Gareth B Gillard, Chris M Brown, Roger P Hellens, Richard C Macknight
BACKGROUND: Transcription factors (TFs) coordinate precise gene expression patterns that give rise to distinct phenotypic outputs. The identification of genes and transcriptional networks regulated by a TF often requires stable transformation and expression changes in plant cells. However, the production of stable transformants can be slow and laborious with no guarantee of success. Furthermore, transgenic plants overexpressing a TF of interest can present pleiotropic phenotypes and/or result in a high number of indirect gene expression changes...
2016: Plant Methods
Lianghua Bin, Donald Y M Leung
BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory disease caused by the complex interaction of genetic, immune and environmental factors. There have many recent discoveries involving the genetic and epigenetic studies of AD. METHODS: A retrospective PubMed search was carried out from June 2009 to June 2016 using the terms "atopic dermatitis", "association", "eczema", "gene", "polymorphism", "mutation", "variant", "genome wide association study", "microarray" "gene profiling", "RNA sequencing", "epigenetics" and "microRNA"...
2016: Allergy, Asthma, and Clinical Immunology
Chao-Jun Hu, Jian-Bo Pan, Guang Song, Xiao-Ting Wen, Zi-Yan Wu, Si Chen, Wen-Xiu Mo, Feng-Chun Zhang, Jiang Qian, Heng Zhu, Yong-Zhe Li
Behcet disease (BD) is a chronic systemic vasculitis and considered as an autoimmune disease. Although rare, BD can be fatal due to ruptured vascular aneurysms or severe neurological complications. To date, no known biomarker has been reported for this disease, making it difficult to diagnosis in the clinics. To undertake this challenge, we employed the HuProt arrays, each comprised of~20,000 unique human proteins, to identify BD-specific autoantibodies using a Two-Phase strategy established previously. In Phase I, we profiled the autoimmunity on the HuProt arrays with 75 serum samples collected from 40 BD patients, 15 diagnosed autoimmune patients who suffer from Takayasu arteritis (TA; N=5)), ANCA associated vasculitis(AAV; N=5), and Sjogren's syndrome(SS; N=5), and 20 healthy subjects, and identified 20 candidate autoantigens that were significantly associated with BD...
October 24, 2016: Molecular & Cellular Proteomics: MCP
An Li, Shanzhong Gong, Kenneth A Johnson
Previous measurements of the rates of polymerization and pyrophosphate release with DNA templates showed that pyrophosphate (PPi) dissociation was fast following nucleotide incorporation so that it did not contribute to enzyme specificity (kcat/Km). Here, kinetic parameters governing nucleotide incorporation and PPi release were determined using an RNA template. Compared with a DNA template of the same sequence, the rate of chemistry increased by up to 10-fold (250 vs 24 s-1) while the rate of PPi release decreased to approximate 58 s-1, so that PPi release became the rate-limiting step...
October 24, 2016: Journal of Biological Chemistry
Weijie Ma, Haitao Wang, Wei Jing, Fuling Zhou, Lei Chang, Zhenfei Hong, Hailing Liu, Zhisu Liu, Yufeng Yuan
BACKGROUND: The expression profiles and biological relevance of long non-coding RNA XIST and its activator JPX in hepatocellular carcinoma (HCC) are not well elucidated. We measured JPX and XIST expression levels in HCC, evaluated their clinical significance in HCC progression, and verified their potential as biomarkers for diagnosing HCC. METHODS: JPX and XIST expression in 68 HCC tissues and adjacent normal tissues were evaluated by quantitative reverse transcription-PCR (qRT-PCR); their association with pathologic features and overall survival was analyzed...
October 21, 2016: Clinics and Research in Hepatology and Gastroenterology
Huiting Zhao, Yali Du, Pengfei Gao, Shujie Wang, Jianfang Pan, Yusuo Jiang
Chemosensory genes play a central role in sensing chemical signals and guiding insect behavior. The Chinese honeybee, Apis cerana cerana, is one of the most important insect species in China in terms of resource production, and providing high-quality products for human consumption, and also serves as an important pollinator. Communication and foraging behavior of worker bees is likely linked to a complex chemosensory system. Here, we used transcriptome sequencing on adult A. c. cerana workers of different ages to identify the major chemosensory gene families and the differentially expressed genes(DEGs), and to investigate their expression profiles...
2016: PloS One
F Chen, Y Zhang, E Parra, J Rodriguez, C Behrens, R Akbani, Y Lu, J M Kurie, D L Gibbons, G B Mills, I I Wistuba, C J Creighton
Non-small-cell lung cancer (NSCLC) demonstrates remarkable molecular diversity. With the completion of The Cancer Genome Atlas (TCGA), there is opportunity for systematic analyses of the entire TCGA NSCLC cohort, including comparisons and contrasts between different disease subsets. On the basis of multidimensional and comprehensive molecular characterization (including DNA methylation and copy, and RNA and protein expression), 1023 NSCLC cases-519 from TCGA adenocarcinoma (AD) project and 504 from TCGA squamous cell carcinoma (SQCC) project-were classified using a 'cluster-of-clusters' analytic approach...
October 24, 2016: Oncogene
Sulev Kõks, Maris Keermann, Ene Reimann, Ele Prans, Kristi Abram, Helgi Silm, Gea Kõks, Kulli Kingo
BACKGROUND: Several studies have been published that investigated potential links between transcriptome changes and psoriasis using microarrays and RNA-seq technologies, but no previous study has analyzed expression profile of alternatively spliced transcripts in psoriasis. OBJECTIVES: Identification of potential alternatively spliced RNA isoforms with disease-specific expression profile. METHODS: Using our published RNA sequencing data from lesional psoriatic (LP), non-lesional psoriatic (NLP), and normal control skin (C), we analyzed the differential expression of RNA splicing variants...
2016: Frontiers in Medicine
Lize Cuypers, Guangdi Li, Christoph Neumann-Haefelin, Supinya Piampongsant, Pieter Libin, Kristel Van Laethem, Anne-Mieke Vandamme, Kristof Theys
Despite significant progress in hepatitis C (HCV) treatment, global viral eradication remains a challenge. An in-depth map of its genome diversity within the context of structural and immunological constraints could contribute to the design of pan-genotypic antivirals and preventive vaccines. For such analyses, extensive information is only available for the highly prevalent HCV genotypes (GT) 1a and 1b. Using 647 GT1a and 408 GT1b full-genome sequences obtained from the Los Alamos database, we found that respectively 3 per cent and 82 per cent of all codon positions are under positive and negative selective pressure, suggesting variation mainly accumulates due to random genetic drift...
July 2016: Virus Evolution
Koichi Wakabayashi, Fumiaki Mori, Akiyoshi Kakita, Hitoshi Takahashi, Shinya Tanaka, Jun Utsumi, Hidenao Sasaki
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression. Recently, we have shown that informative miRNA data can be derived from archived formalin-fixed paraffin-embedded (FFPE) samples from postmortem cases of amyotrophic lateral sclerosis and normal controls. miRNA analysis has now been performed on FFPE samples from affected brain regions in patients with multiple system atrophy (MSA) and the same areas in neurologically normal controls. We evaluated 50 samples from patients with MSA (n=13) and controls (n=13)...
October 20, 2016: Neuroscience Letters
Gianluigi Lichinchi, Boxuan Simen Zhao, Yinga Wu, Zhike Lu, Yue Qin, Chuan He, Tariq M Rana
Infection with the flavivirus Zika (ZIKV) causes neurological, immunological, and developmental defects through incompletely understood mechanisms. We report that ZIKV infection affects viral and human RNAs by altering the topology and function of N(6)-adenosine methylation (m(6)A), a modification affecting RNA structure and function. m(6)A nucleosides are abundant in ZIKV RNA, with twelve m(6)A peaks identified across full-length ZIKV RNA. m(6)A in ZIKV RNA is controlled by host methyltransferases METTL3 and METTL14 and demethylases ALKBH5 and FTO, and knockdown of methyltransferases increases, while silencing demethylases decreases, ZIKV production...
October 18, 2016: Cell Host & Microbe
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