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Saiful Islam, Masashi Ueda, Emika Nishida, Miao-Xing Wang, Masatake Osawa, Dongsoo Lee, Masanori Itoh, Kiyomi Nakagawa, Tana, Toshiyuki Nakagawa
Olfaxin, which is a BNIP2 and Cdc42GAP homology (BCH) domain-containing protein, is predominantly expressed in mitral and tufted (M/T) cells in the olfactory bulb (OB). Olfaxin and Caytaxin, which share 56.3% amino acid identity, are similar in their glutamatergic terminal localization, kidney-type glutaminase (KGA) interaction, and caspase-3 substrate. Although the deletion of Caytaxin protein causes human Cayman ataxia and ataxia in the mutant mouse, the function of Olfaxin is largely unknown. In this study, we generated Prune2 gene mutant mice (Prune2Ex16-/- ; knock out [KO] mice) using the CRISPR/Cas9 system, during which the exon 16 containing start codon of Olfaxin mRNA was deleted...
March 20, 2018: Brain Research
Filomena Cetani, Elena Pardi, Claudio Marcocci
Parathyroid carcinoma (PC) is a rare neoplasia difficult to diagnose preoperatively. It mainly occurs as a sporadic disease but also as part of familial PHPT. At variance with patients with the benign counterpart, the phenotype of these patients is characterized by a severe primary hyperparathyroidism (PHPT). The clinical features are mostly due to the effects of the excessive secretion of PTH by the functioning tumor and hypercalcemia rather than to the tumor burden. The prognosis is poor and unmanageable hypercalcemia accounts for death in the majority of cases...
September 25, 2017: Minerva Endocrinologica
Mrudhula Anuppalle, Sateesh Maddirevula, Ajeet Kumar, Tae-Lin Huh, Joonho Choe, Myungchull Rhee
PRUNE2 has been identified as a susceptible gene for Alzheimer's disease and a marker for leiomyosarcomas. Isoforms of Prune2 regulate neuronal cell differentiation and synaptogenesis. Although expression pattern of Prune2 has been reported in the murine brain, its expression patterns and regulation along vertebrate embryogenesis remain to be further investigated. We thus defined the expression profiles and transcriptional regulation of prune2 in zebrafish embryos. prune2 exhibits maternal expression, but is increased in later embryonic stages, and expressed in the telencephalon, epiphysis cluster, nucleus of the tract of the post optic commissure, spinal cord, cerebellum, tegmentum, anterior lateral line ganglion, posterior lateral line ganglion and rhombomeres 2 through 5...
January 2017: Gene Expression Patterns: GEP
Mathilde Cheray, Barbara Bessette, Aurélie Lacroix, Carole Mélin, Soha Jawhari, Sandra Pinet, Elise Deluche, Pierre Clavère, Karine Durand, Ricardo Sanchez-Prieto, Marie-Odile Jauberteau, Serge Battu, Fabrice Lalloué
Glioblastoma is the most lethal brain tumour with a poor prognosis. Cancer stem cells (CSC) were proposed to be the most aggressive cells allowing brain tumour recurrence and aggressiveness. Current challenge is to determine CSC signature to characterize these cells and to develop new therapeutics. In a previous work, we achieved a screening of glycosylation-related genes to characterize specific genes involved in CSC maintenance. Three genes named CHI3L1, KLRC3 and PRUNE2 were found overexpressed in glioblastoma undifferentiated cells (related to CSC) compared to the differentiated ones...
February 2017: Journal of Cellular and Molecular Medicine
Mohammad Sazzadul Islam, Yasutoshi Tatsumi, Ryo Takano, Tomoki Yokochi, Jesmin Akter, Toshinori Ozaki, Yohko Nakamura, Miki Ohira, Akira Nakagawara
BCH motif-containing molecule at the carboxyl terminal region 1 (BMCC1)/PRUNE2 is highly expressed in patients with favorable neuroblastoma (NB), encoding a multifunctional scaffold protein that modulates several signaling networks including RhoA and AKT pathways. Accumulating evidence suggests that BMCC1 acts as a tumor-suppressor. In this study, we addressed molecular mechanism underlying transcriptional regulation of BMCC1 in NBs. We found that transcription factor E2F1 was recruited to E2F-binding site in the promoter region of BMCC1 gene...
September 9, 2016: Biochemical and Biophysical Research Communications
Paul William Harms, Pankaj Vats, Monique Elise Verhaegen, Dan R Robinson, Yi-Mi Wu, Saravana Mohan Dhanasekaran, Nallasivam Palanisamy, Javed Siddiqui, Xuhong Cao, Fengyun Su, Rui Wang, Hong Xiao, Lakshmi P Kunju, Rohit Mehra, Scott A Tomlins, Douglas Randall Fullen, Christopher Keram Bichakjian, Timothy M Johnson, Andrzej Antoni Dlugosz, Arul M Chinnaiyan
Merkel cell carcinoma (MCC) is a rare but highly aggressive cutaneous neuroendocrine tumor. Merkel cell polyomavirus (MCPyV) may contribute to tumorigenesis in a subset of tumors via inhibition of tumor suppressors such as retinoblastoma (RB1) by mutated viral T antigens, but the molecular pathogenesis of MCPyV-negative MCC is largely unexplored. Through our MI-ONCOSEQ precision oncology study, we performed integrative sequencing on two cases of MCPyV-negative MCC, as well as a validation cohort of 14 additional MCC cases (n = 16)...
September 15, 2015: Cancer Research
Ahmad Salameh, Alessandro K Lee, Marina Cardó-Vila, Diana N Nunes, Eleni Efstathiou, Fernanda I Staquicini, Andrey S Dobroff, Serena Marchiò, Nora M Navone, Hitomi Hosoya, Richard C Lauer, Sijin Wen, Carolina C Salmeron, Anh Hoang, Irene Newsham, Leandro A Lima, Dirce M Carraro, Salvatore Oliviero, Mikhail G Kolonin, Richard L Sidman, Kim-Anh Do, Patricia Troncoso, Christopher J Logothetis, Ricardo R Brentani, George A Calin, Webster K Cavenee, Emmanuel Dias-Neto, Renata Pasqualini, Wadih Arap
Prostate cancer antigen 3 (PCA3) is the most specific prostate cancer biomarker but its function remains unknown. Here we identify PRUNE2, a target protein-coding gene variant, which harbors the PCA3 locus, thereby classifying PCA3 as an antisense intronic long noncoding (lnc)RNA. We show that PCA3 controls PRUNE2 levels via a unique regulatory mechanism involving formation of a PRUNE2/PCA3 double-stranded RNA that undergoes adenosine deaminase acting on RNA (ADAR)-dependent adenosine-to-inosine RNA editing...
July 7, 2015: Proceedings of the National Academy of Sciences of the United States of America
Hanna Janke, Friederike Pastore, Daniela Schumacher, Tobias Herold, Karl-Peter Hopfner, Stephanie Schneider, Wolfgang E Berdel, Thomas Büchner, Bernhard J Woermann, Marion Subklewe, Stefan K Bohlander, Wolfgang Hiddemann, Karsten Spiekermann, Harald Polzer
About 30% of patients with acute myeloid leukemia (AML) harbour mutations of the receptor tyrosine kinase FLT3, mostly internal tandem duplications (ITD) and point mutations of the second tyrosine kinase domain (TKD). It was the aim of this study to comprehensively analyze clinical and functional properties of various FLT3 mutants. In 672 normal karyotype AML patients FLT3-ITD, but not FLT3-TKD mutations were associated with a worse relapse free and overall survival in multivariate analysis. In paired diagnosis-relapse samples FLT3-ITD showed higher stability (70%) compared to FLT3-TKD (30%)...
2014: PloS One
Yan Song, Jinsoo Ahn, Yeunsu Suh, Michael E Davis, Kichoon Lee
Understanding the tissue-specific pattern of gene expression is critical in elucidating the molecular mechanisms of tissue development, gene function, and transcriptional regulations of biological processes. Although tissue-specific gene expression information is available in several databases, follow-up strategies to integrate and use these data are limited. The objective of the current study was to identify and evaluate novel tissue-specific genes in human and mouse tissues by performing comparative microarray database analysis and semi-quantitative PCR analysis...
2013: PloS One
Lin-Ru Zhao, Wei Tian, Guo-Wen Wang, Ke-Xin Chen, Ji-Long Yang
PRUNE2 plays an important role in regulating tumor cell differentiation, proliferation, and invasiveness in neuroblastoma. Our previous study revealed that PRUNE2/OBSCN two-gene relative expression classifer accurately differentiated leiomyosarcoma from gastrointestinal stromal tumor. However, the association between PRUNE2 expression and prognosis in leiomyosarcoma is poorly understood. In this study, we evaluated the prognostic role of PRUNE2 in leiomyosarcoma. PRUNE2 expression was detected using immunohistochemistry in 30 formalin-fixed, paraffin-embedded leiomyosarcoma tissues from MD Anderson Cancer Center, and high expression was detected in 36...
December 2013: Chinese Journal of Cancer
Shimo Li, Yoshika Hayakawa-Yano, Masanori Itoh, Masashi Ueda, Kazunori Ohta, Yoshihiro Suzuki, Akihito Mizuno, Eri Ohta, Yoko Hida, Miao-Xing Wang, Toshiyuki Nakagawa
Prune homolog 2 (Drosophila) (PRUNE2) encodes a BCH motif-containing protein that shares homology with the Cayman ataxia-related protein Caytaxin. Caytaxin is a substrate of caspase-3 and is specifically expressed at the presynapse of vesicular-type glutamate transporter (VGLUT)-positive neurons, where it plays a role in glutamate neurotransmission primarily in the cerebellum and hippocampus. Here, we showed that a novel Prune2 isoform contains a BCH motif and localizes predominantly to the synaptic cytosol, similar to Caytaxin...
December 7, 2012: Brain Research
Ji-long Yang, David Cogdell, James Eddy, Jonathan Trent, Nathan Price, Wei Zhang
OBJECTIVE: Our previous study shows that PURNE2 mRNA plays an important role in the differential diagnosis of leiomyosarcoma and gastrointestinal stromal tumor (GIST). Non-coding RNA PCA3 locates in the intron of PRUNE2 and may play a role in PRUNE2 expression. The aim of this study was to explore the expression of PCA3 mRNA and PRUNE2 in leiomyosarcoma and their correlation. METHODS: The expression of PRUNE2 mRNA was analyzed by agilent gene expression microarray CHIP in 31 leiomyosarcomas and 37 GISTs, and the correlation of the PRUNE2 expression and prognosis of leiomyosarcoma was predicted...
July 2012: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
Irene Hinterseher, Robert Erdman, James R Elmore, Elizabeth Stahl, Matthew C Pahl, Kimberly Derr, Alicia Golden, John H Lillvis, Matthew C Cindric, Kathryn Jackson, William D Bowen, Charles M Schworer, Michael A Chernousov, David P Franklin, John L Gray, Robert P Garvin, Zoran Gatalica, David J Carey, Gerard Tromp, Helena Kuivaniemi
OBJECTIVES: Abdominal aortic aneurysm (AAA), a dilatation of the infrarenal aorta, typically affects males >65 years. The pathobiological mechanisms of human AAA are poorly understood. The goal of this study was to identify novel pathways involved in the development of AAAs. METHODS: A custom-designed 'AAA-chip' was used to assay 43 of the differentially expressed genes identified in a previously published microarray study between AAA (n = 15) and control (n = 15) infrarenal abdominal aorta...
2013: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Jessica Arama, Anne-Cécile Boulay, Christophe Bosc, Christian Delphin, Damarys Loew, Philippe Rostaing, Edwige Amigou, Pascal Ezan, Laure Wingertsmann, Laurent Guillaud, Annie Andrieux, Christian Giaume, Martine Cohen-Salmon
The BCH (BNIP2 and Cdc42GAP Homology) domain-containing protein Bmcc1/Prune2 is highly enriched in the brain and is involved in the regulation of cytoskeleton dynamics and cell survival. However, the molecular mechanisms accounting for these functions are poorly defined. Here, we have identified Bmcc1s, a novel isoform of Bmcc1 predominantly expressed in the mouse brain. In primary cultures of astrocytes and neurons, Bmcc1s localized on intermediate filaments and microtubules and interacted directly with MAP6/STOP, a microtubule-binding protein responsible for microtubule cold stability...
2012: PloS One
Shimo Li, Masanori Itoh, Kazunori Ohta, Masashi Ueda, Akihito Mizuno, Eri Ohta, Yoko Hida, Miao-Xing Wang, Kazunori Takeuchi, Toshiyuki Nakagawa
A family of Bcl-2/adenovirus E1B 19kDa-interacting proteins (BNIPs) plays critical roles in several cellular processes such as cellular transformation, apoptosis, neuronal differentiation, and synaptic function, which are mediated by the BNIP2 and Cdc42GAP homology (BCH) domain. Prune homolog 2 (Drosophila) (PRUNE2) and its isoforms -C9orf65, BCH motif-containing molecule at the carboxyl terminal region 1 (BMCC1), and BNIP2 Extra Long (BNIPXL) - have been shown to be a susceptibility gene for Alzheimer's disease, a biomarker for leiomyosarcomas, a proapoptotic protein in neuronal cells, and an antagonist of cellular transformation, respectively...
October 10, 2011: Neuroscience Letters
Eiji Iwama, Daisuke Tsuchimoto, Teruaki Iyama, Kunihiko Sakumi, Akira Nakagawara, Koichi Takayama, Yoichi Nakanishi, Yusaku Nakabeppu
Human PRUNE is thought to enhance the metastasis of tumor cells. We found that a hypothetical paralog of PRUNE, PRUNE2, binds to 8-oxo-GTP, an oxidized form of GTP. Hypothetical PRUNE2 gene consists of C9orf65 and BMCC1/BNIPXL, both of which are malignant tumor-associated genes. We isolated PRUNE2 complementary DNA and revealed that the protein is composed of 3,062 residues. C9orf65 and BMCC1/BNIPXL encode the N-terminal part (259 residues) and C-terminal part (2,729 residues) of PRUNE2, respectively. We demonstrated the endogenous full-length PRUNE2 protein (338 kDa) by Western blot and mass spectrometry...
June 2011: Journal of Molecular Neuroscience: MN
Maciej Salagierski, Gerald W Verhaegh, Sander A Jannink, Frank P Smit, Daphne Hessels, Jack A Schalken
BACKGROUND: PCA3 is one of the most prostate cancer (PrCa)-specific markers described so far. Recently, a new genomic structure of PCA3 as well as new flanking and overlapping gene transcripts has been identified. Furthermore, a co-regulation of PCA3 and its overlapping gene PRUNE2(BMCC1) has been suggested. Our aim was to assess the diagnostic performance of a new PCA3 isoform (PCA3-TS4) and to study the interactions between PCA3 and BMCC1 in PrCa. METHODS: We used SYBR Green quantitative (q)PCR with specific primers to compare PCA3 and BMCC1 expression of normal versus tumor tissue of human prostate...
January 1, 2010: Prostate
Steven G Potkin, Guia Guffanti, Anita Lakatos, Jessica A Turner, Frithjof Kruggel, James H Fallon, Andrew J Saykin, Alessandro Orro, Sara Lupoli, Erika Salvi, Michael Weiner, Fabio Macciardi
BACKGROUND: With the exception of APOE epsilon4 allele, the common genetic risk factors for sporadic Alzheimer's Disease (AD) are unknown. METHODS AND FINDINGS: We completed a genome-wide association study on 381 participants in the ADNI (Alzheimer's Disease Neuroimaging Initiative) study. Samples were genotyped using the Illumina Human610-Quad BeadChip. 516,645 unique Single Nucleotide Polymorphisms (SNPs) were included in the analysis following quality control measures...
August 7, 2009: PloS One
Raymond A Clarke, Zhongming Zhao, An-Yuan Guo, Kathrein Roper, Linda Teng, Zhi-Ming Fang, Hema Samaratunga, Martin F Lavin, Robert A Gardiner
BACKGROUND: The prostate cancer antigen 3 (PCA3/DD3) gene is a highly specific biomarker upregulated in prostate cancer (PCa). In order to understand the importance of PCA3 in PCa we investigated the organization and evolution of the PCA3 gene locus. METHODS/PRINCIPAL FINDINGS: We have employed cDNA synthesis, RTPCR and DNA sequencing to identify 4 new transcription start sites, 4 polyadenylation sites and 2 new differentially spliced exons in an extended form of PCA3...
2009: PloS One
T G Wilson, K B Jacobson
The suppressible eye color mutant purple (pr) of Drosophila melanogaster is known to be unable to synthesize a wild-type complement of pteridine eye pigments. This study measures the reduced levels of drosopterins, sepiapterin, and an unidentified presumed pteridine in pr and prbw. Pteridine analyses in double mutants combining pr with one of three other eye color mutants sepia, Henna-recessive3, and prune2, suggest that the metabolic block in pr occurs prior to sepiapterin biosynthesis. Measurements of GTP and GTP cyclohydrolase in pr showed wild-type levels and indicate the metabolic block in pr to be at one of the steps converting dihydroneopterin triphosphate to sepiapterin...
April 1977: Biochemical Genetics
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