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https://www.readbyqxmd.com/read/27925341/skeletal-muscle-atrophy-is-induced-by-fbxw7%C3%AE-via-atrogene-upregulation
#1
Kyungshin Shin, Young-Gyu Ko, Jaemin Jeong, Heechung Kwon
Muscle atrophy decreases skeletal muscle mass and is induced by inherited cachectic symptoms, genetic disorders, and sarcopenia. However, the molecular pathways associated with the onset of muscle atrophy are still unclear. In this study, we evaluated Fbxw7β, a gene associated with the development of muscle atrophy in vitro and in vivo. Among the three Fbxw7 isoforms, ectopically overexpressed Fbxw7β induced the expression of myogenin and major atrogene markers (atrogin-1 and MuRF-1) and reduced myoblast differentiation...
December 7, 2016: Cell Biology International
https://www.readbyqxmd.com/read/27904771/tumor-suppressive-function-of-long-noncoding-rna-malat1-in-glioma-cells-by-suppressing-mir-155-expression-and-activating-fbxw7-function
#2
Shuanzhu Cao, Yanzhou Wang, Jinquan Li, Mingliang Lv, Haitao Niu, Yong Tian
The human metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA associated with metastasis, and is a favorable prognostic factor for lung cancer. Recent studies have shown that MALAT1 plays an important role in many malignancies. However, little is known about the role of MALAT1 in glioma. In this study, we determined the expression of MALAT1 and explored its prognostic value in glioma. Further, we investigated the regulatory mechanism of MALAT1 in glioma progression. Our results showed that the expression of MALAT1 was significantly decreased in glioma specimens than in noncancerous brain tissues...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27900032/mir-223-decreases-cell-proliferation-and-enhances-cell-apoptosis-in-acute-myeloid-leukemia-via-targeting-fbxw7
#3
Yi Xiao, Changliang Su, Taoran Deng
The expression of microRNA-223 (miR-233) has been investigated in various types of cancer. However, to the best of our knowledge, the expression and function of miR-223 in acute myeloid leukemia (AML) remains to be elucidated. The expression of miR-223 was measured by reverse transcription-quantitative polymerase chain reaction. Following transfection with miR-223, cell viability assays, cell apoptosis assays, western blot analysis and luciferase assays were conducted in AML cell lines. In the present study, it was initially observed that miR-223 was downregulated in AML patients compared with healthy subjects...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27890934/egr2-mutations-define-a-new-clinically-aggressive-subgroup-of-chronic-lymphocytic-leukemia
#4
E Young, D Noerenberg, L Mansouri, V Ljungström, M Frick, L-A Sutton, S J Blakemore, J Galan-Sousa, K Plevova, P Baliakas, D Rossi, R Clifford, D Roos-Weil, V Navrkalova, B Dörken, C A Schmitt, K E Smedby, G Juliusson, B Giacopelli, J S Blachly, C Belessi, P Panagiotidis, N Chiorazzi, F Davi, A W Langerak, D Oscier, A Schuh, G Gaidano, P Ghia, W Xu, L Fan, O A Bernard, F Nguyen-Khac, L Rassenti, J Li, T J Kipps, K Stamatopoulos, S Pospisilova, T Zenz, C C Oakes, J C Strefford, R Rosenquist, F Damm
Recurrent mutations within EGR2 were recently reported in advanced-stage chronic lymphocytic leukemia (CLL) patients and associated with a worse outcome. To study their prognostic impact, 2403 CLL patients were examined for mutations in the EGR2 hotspot region including a screening (n=1283) and two validation cohorts (UK CLL4 trial patients, n=366; CLL Research Consortium (CRC) patients, n=490). Targeted deep-sequencing of 27 known/postulated CLL driver genes was also performed in 38 EGR2-mutated patients to assess concurrent mutations...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27852700/genomic-evolution-after-chemoradiotherapy-in-anal-squamous-cell-carcinoma
#5
Kent W Mouw, James M Cleary, Brendan Reardon, Jonathan Pike, Lior Z Braunstein, Jaegil Kim, Ali Amin-Mansour, Diana Miao, Alexis Damish, Joanna Chin, Patrick A Ott, Charles S Fuchs, Neil E Martin, Gad Getz, Scott Carter, Harvey Mamon, Jason L Hornick, Eliezer Van Allen, Alan D D'Andrea
PURPOSE: Squamous cell carcinoma of the anal canal (ASCC) accounts for 2-4% of gastrointestinal (GI) malignancies in the US and is increasing in incidence; however, genomic features of ASCC are incompletely characterized. Primary treatment of ASCC involves concurrent chemotherapy and radiation (CRT), but the mutational landscape of resistance to CRT is unknown. Here, we aim to compare mutational features of ASCC in the pre- and post-CRT setting. EXPERIMENTAL DESIGN: We perform whole exome sequencing of primary (n=31) and recurrent (n=31) ASCCs and correlate findings with clinical data...
November 16, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27837025/structural-basis-of-n-myc-binding-by-aurora-a-and-its-destabilization-by-kinase-inhibitors
#6
Mark W Richards, Selena G Burgess, Evon Poon, Anne Carstensen, Martin Eilers, Louis Chesler, Richard Bayliss
Myc family proteins promote cancer by inducing widespread changes in gene expression. Their rapid turnover by the ubiquitin-proteasome pathway is regulated through phosphorylation of Myc Box I and ubiquitination by the E3 ubiquitin ligase SCF(FbxW7) However, N-Myc protein (the product of the MYCN oncogene) is stabilized in neuroblastoma by the protein kinase Aurora-A in a manner that is sensitive to certain Aurora-A-selective inhibitors. Here we identify a direct interaction between the catalytic domain of Aurora-A and a site flanking Myc Box I that also binds SCF(FbxW7) We determined the crystal structure of the complex between Aurora-A and this region of N-Myc to 1...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27822062/dysfunction-of-microrna-32-regulates-ubiquitin-ligase-fbxw7-in-multiple-myeloma-disease
#7
Jingsheng Hua, Tianling Ding, Linjun Yang
Dysfunction of microRNA (miRNA) expression has been associated with tumor occurrence, progression, and development. The aim of this work was to study the dysfunction of miR-32 - an miRNA that was abnormally regulated in different tumors - in clinical tissues from patients with multiple myeloma (MM). The tumor tissues in which we assessed miR-32 expression levels were collected during our 5 years of clinical practice. Our study found an increase in miR-32 expression in MM tissues. Assessment of F-box and WD repeat domain-containing 7 (FBXW7) in MM tissues showed an inverse relation between the expression of FBXW7 and miR-32...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27812198/visceral-adipose-microrna-223-is-upregulated-in-human-and-murine-obesity-and-modulates-the-inflammatory-phenotype-of-macrophages
#8
Jeffrey A Deiuliis, Rafay Syed, Dheeraj Duggineni, Jessica Rutsky, Palanivel Rengasamy, Jie Zhang, Kun Huang, Bradley Needleman, Dean Mikami, Kyle Perry, Jeffrey Hazey, Sanjay Rajagopalan
Obesity in humans and mice is typified by an activated macrophage phenotype in the visceral adipose tissue (VAT) leading to increased macrophage-mediated inflammation. microRNAs (miRNAs) play an important role in regulating inflammatory pathways in macrophages, and in this study we compared miRNA expression in the VAT of insulin resistant morbidly obese humans to a non-obese cohort with normal glucose tolerance. miR-223-3p was found to be significantly upregulated in the whole omental tissue RNA of 12 human subjects, as were 8 additional miRNAs...
2016: PloS One
https://www.readbyqxmd.com/read/27764699/fbxw7-deletion-accelerates-kras-g12d-driven-pancreatic-tumorigenesis-via-yap-accumulation
#9
Qiang Zhang, Yaqing Zhang, Joshua D Parsels, Ines Lohse, Theodore S Lawrence, Marina Pasca di Magliano, Yi Sun, Meredith A Morgan
Pancreatic cancers driven by KRAS mutations require additional mutations for tumor progression. The tumor suppressor FBXW7 is altered in pancreatic cancers, but its contribution to pancreatic tumorigenesis is unknown. To determine potential cooperation between Kras mutation and Fbxw7 inactivation in pancreatic tumorigenesis, we generated P48-Cre;LSL-Kras(G12D);Fbxw7(fl/fl) (KFC(fl/fl)) compound mice. We found that KFC(fl/fl) mice displayed accelerated tumorigenesis: all mice succumbed to pancreatic ductal adenocarcinoma (PDA) by 40 days of age, with PDA onset occurring by 2 weeks of age...
November 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27759908/translocation-t-8-14-q24-q11-with-concurrent-pten-alterations-and-deletions-of-stil-tal1-and-cdkn2a-b-in-a-pediatric-case-of-acute-t-lymphoblastic-leukemia-a-genetic-profile-associated-with-adverse-prognosis
#10
Jolanta Skalska-Sadowska, Małgorzata Dawidowska, Bronisława Szarzyńska-Zawadzka, Małgorzata Jarmuż-Szymczak, Joanna Czerwińska-Rybak, Ludomiła Machowska, Katarzyna Derwich
We report a pediatric case of acute T-lymphoblastic leukemia (T-ALL) with NOTCH1(wt) , FBXW7(wt) , STIL/TAL1, and PTEN (exons 2, 3, 4, 5) monoallelic deletions, biallelic CDKN2A/B deletion, and a minor t(8;14)(q24;q11)-positive subclone. Undetectable by a flow cytometric minimal residual disease assay, the t(8;14)(q24;q11) subclone expanded as detected by fluorescence in situ hybridization from 5% at diagnosis to 26% before consolidation and 100% at relapse bearing a monoallelic deletion (exons 2, 3) with a new frameshift mutation of PTEN and the same set of remaining molecular alterations...
October 19, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27756406/spatio-temporal-mutation-profiles-of-case-matched-colorectal-carcinomas-and-their-metastases-reveal-unique-de-novo-mutations-in-metachronous-lung-metastases-by-targeted-next-generation-sequencing
#11
Valentina Kovaleva, Anna-Lena Geissler, Lisa Lutz, Ralph Fritsch, Frank Makowiec, Sebastian Wiesemann, Ulrich T Hopt, Bernward Passlick, Martin Werner, Silke Lassmann
BACKGROUND: Targeted next generation sequencing (tNGS) has become part of molecular pathology diagnostics for determining RAS mutation status in colorectal cancer (CRC) patients as predictive tool for decision on EGFR-targeted therapy. Here, we investigated mutation profiles of case-matched tissue specimens throughout the disease course of CRC, to further specify RAS-status dynamics and to identify de novo mutations associated with distant metastases. METHODS: Case-matched formalin-fixed and paraffin-embedded (FFPE) resection specimens (n = 70; primary tumours, synchronous and/or metachronous liver and/or lung metastases) of 14 CRC cases were subjected to microdissection of normal colonic epithelial, primary and metastatic tumour cells, their DNA extraction and an adapted library protocol for limited DNA using the 48 gene TruSeq Amplicon Cancer Panel(TM), MiSeq sequencing and data analyses (Illumina)...
October 18, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27734031/subtyping-sub-saharan-esophageal-squamous-cell-carcinoma-by-comprehensive-molecular-analysis
#12
Wenjin Liu, Jeff M Snell, William R Jeck, Katherine A Hoadley, Matthew D Wilkerson, Joel S Parker, Nirali Patel, Yohannie B Mlombe, Gift Mulima, N George Liomba, Lindsey L Wolf, Carol G Shores, Satish Gopal, Norman E Sharpless
Esophageal squamous cell carcinoma (ESCC) is endemic in regions of sub-Saharan Africa (SSA), where it is the third most common cancer. Here, we describe whole-exome tumor/normal sequencing and RNA transcriptomic analysis of 59 patients with ESCC in Malawi. We observed similar genetic aberrations as reported in Asian and North American cohorts, including mutations of TP53, CDKN2A, NFE2L2, CHEK2, NOTCH1, FAT1, and FBXW7. Analyses for nonhuman sequences did not reveal evidence for infection with HPV or other occult pathogens...
October 6, 2016: JCI Insight
https://www.readbyqxmd.com/read/27729614/genomic-profiling-of-stage-ii-and-iii-colon-cancers-reveals-apc-mutations-to-be-associated-with-survival-in-stage-iii-colon-cancer-patients
#13
Evert van den Broek, Oscar Krijgsman, Daoud Sie, Marianne Tijssen, Sandra Mongera, Mark A van de Wiel, Eric J. Belt, Sjoerd H den Uil, Herman Bril, Hein B A C Stockmann, Bauke Ylstra, Beatriz Carvalho, Gerrit A Meijer, Remond J A Fijneman
Tumor profiling of DNA alterations, i.e. gene point mutations, somatic copy number aberrations (CNAs) and structural variants (SVs), improves insight into the molecular pathology of cancer and clinical outcome. Here, associations between genomic aberrations and disease recurrence in stage II and III colon cancers were investigated. A series of 114 stage II and III microsatellite stable colon cancer samples were analyzed by high-resolution array-comparative genomic hybridization (array-CGH) to detect CNAs and CNA-associated chromosomal breakpoints (SVs)...
October 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/27704356/microrna-27b-exerts-an-oncogenic-function-by-targeting-fbxw7-in-human-hepatocellular-carcinoma
#14
Xin-Fang Sun, Jin-Ping Sun, Hong-Tao Hou, Ke Li, Xin Liu, Quan-Xing Ge
Aberrant expression of microRNAs (miRNAs) plays fundamental effect on the pathogenesis of hepatocellular carcinoma (HCC). MiR-27b was previously found to play important roles in human cancers. However, its expression status, clinical significance, and biological functions in HCC remain largely unclear. The expression status of miR-27b in HCC specimens and cells were determined with qRT-PCR. MTT, 5-bromodeoxyuridine (BrdU) proliferation assays, and flow cytometry analysis were carried out to assay proliferation, cell cycle, and apoptosis...
October 4, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27687303/mutation-profiles-in-early-stage-lung-squamous-cell-carcinoma-with-clinical-follow-up-and-correlation-with-markers-of-immune-function
#15
M Choi, H Kadara, J Zhang, E P Cuentas, J R Canales, S G Gaffney, Z Zhao, C Behrens, J Fujimoto, C Chow, K Kim, N Kalhor, C Moran, D Rimm, S Swisher, D L Gibbons, J Heymach, E Kaftan, J P Townsend, T J Lynch, J Schlessinger, J Jack Lee, R P Lifton, R S Herbst, I I Wistuba
BACKGROUND: Lung squamous cell carcinoma (LUSC) accounts for 20-30% of non-small cell lung cancers (NSCLCs). There are limited treatment strategies for LUSC in part due to our inadequate understanding of the molecular underpinnings of the disease. We performed whole-exome sequencing (WES) and comprehensive immune profiling of a unique set of clinically annotated early-stage LUSCs to increase our understanding of the pathobiology of this malignancy. METHODS: Matched pairs of surgically resected stage I-III LUSCs and normal lung tissues (n=108) were analyzed by WES...
September 29, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27648365/mir-182-promotes-proliferation-and-invasion-and-elevates-the-hif-1%C3%AE-vegf-a-axis-in-breast-cancer-cells-by-targeting-fbxw7
#16
Chi-Hsiang Chiang, Pei-Yi Chu, Ming-Feng Hou, Wen-Chun Hung
The feature of imperfect complementary effect of miRNAs to mRNAs implies that miRNAs may simultaneously target different mRNAs to affect multiple aspects of tumorigenesis. In our previous results, we demonstrated that miR-182 was over-expressed in breast cancer cell lines and clinical tumor tissues and its up-regulation increased tumorigenicity and invasiveness by repressing a tumor suppressor RECK. In this study, we showed that overexpression miR-182 regulated actin distribution and filopodia formation to increase invasiveness of breast cancer cells...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27633522/extensive-next-generation-sequencing-analysis-in-chronic-lymphocytic-leukemia-at-diagnosis-clinical-and-biological-correlations
#17
Gian Matteo Rigolin, Elena Saccenti, Cristian Bassi, Laura Lupini, Francesca Maria Quaglia, Maurizio Cavallari, Sara Martinelli, Luca Formigaro, Enrico Lista, Maria Antonella Bardi, Eleonora Volta, Elisa Tammiso, Aurora Melandri, Antonio Urso, Francesco Cavazzini, Massimo Negrini, Antonio Cuneo
BACKGROUND: In chronic lymphocytic leukemia (CLL), next-generation sequencing (NGS) analysis represents a sensitive, reproducible, and resource-efficient technique for routine screening of gene mutations. METHODS: We performed an extensive biologic characterization of newly diagnosed CLL, including NGS analysis of 20 genes frequently mutated in CLL and karyotype analysis to assess whether NGS and karyotype results could be of clinical relevance in the refinement of prognosis and assessment of risk of progression...
September 15, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27609830/subclonal-diversity-arises-early-even-in-small-colorectal-tumours-and-contributes-to-differential-growth-fates
#18
Chelsie K Sievers, Luli S Zou, Perry J Pickhardt, Kristina A Matkowskyj, Dawn M Albrecht, Linda Clipson, Jeffery W Bacher, B Dustin Pooler, Fouad J Moawad, Brooks D Cash, Mark Reichelderfer, Tien N Vo, Michael A Newton, Bret R Larget, Richard B Halberg
OBJECTIVE AND DESIGN: The goal of the study was to determine whether the mutational profile of early colorectal polyps correlated with growth behaviour. The growth of small polyps (6-9 mm) that were first identified during routine screening of patients was monitored over time by interval imaging with CT colonography. Mutations in these lesions with known growth rates were identified by targeted next-generation sequencing. The timing of mutational events was estimated using computer modelling and statistical inference considering several parameters including allele frequency and fitness...
September 8, 2016: Gut
https://www.readbyqxmd.com/read/27602765/genomic-characterization-of-pediatric-t-cell-acute-lymphoblastic-leukemia-reveals-novel-recurrent-driver-mutations
#19
Jean-François Spinella, Pauline Cassart, Chantal Richer, Virginie Saillour, Manon Ouimet, Sylvie Langlois, Pascal St-Onge, Thomas Sontag, Jasmine Healy, Mark D Minden, Daniel Sinnett
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with variable prognosis. It represents 15% of diagnosed pediatric ALL cases and has a threefold higher incidence among males. Many recurrent alterations have been identified and help define molecular subgroups of T-ALL, however the full range of events involved in driving transformation remain to be defined. Using an integrative approach combining genomic and transcriptomic data, we molecularly characterized 30 pediatric T-ALLs and identified common recurrent T-ALL targets such as FBXW7, JAK1, JAK3, PHF6, KDM6A and NOTCH1 as well as novel candidate T-ALL driver mutations including the p...
September 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27594513/fbxw7%C3%AE-e3-ubiquitin-ligase-negative-regulation-of-primary-myoblast-differentiation-proliferation-and-migration
#20
Kyungshin Shin, Sang-Gu Hwang, Ik Joon Choi, Young-Gyu Ko, Jaemin Jeong, Heechung Kwon
Satellite cells attached to skeletal muscle fibers play a crucial role in skeletal muscle regeneration. During regeneration, the satellite cells proliferate, migrate to the damaged region, and fuse to each other. Although it is important to determine the cellular mechanisms controlling myoblast behavior, their regulators are not well understood. In this study, we evaluated the roles of Fbxw7 in primary myoblasts and determined its potential as a therapeutic target for muscle disease. We originally found that Fbxw7β, one of the E3 ubiquitin ligase Fbxw7 subtypes, negatively regulates differentiation, proliferation and migration of myoblasts and satellite cells on muscle fiber...
September 4, 2016: Animal Science Journal, Nihon Chikusan Gakkaihō
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