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          Institute: MPI für Infektionsbiologie     Collection: Core Facilites     Display Documents



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ID: 611217.0, MPI für Infektionsbiologie / Core Facilites
MiR-133b Targets Antiapoptotic Genes and Enhances Death Receptor-Induced Apoptosis
Authors:Patron, Juan Pablo; Fendler, Annika; Bild, Matthias; Jung, Ulrike; Müller, Henrik; Arntzen, Magnus O.; Piso, Chloe; Stephan, Carsten; Thiede, Bernd; Mollenkopf, Hans-Joachim; Jung, Klaus; Kaufmann, Stefan H. E.; Schreiber, Joerg
Date of Publication (YYYY-MM-DD):2012-04-20
Title of Journal:PLoS ONE
Journal Abbrev.:PLoS One
Volume:7
Issue / Number:4
Sequence Number of Article:e35345
Copyright:Copyright Patron et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Review Status:Peer-review
Audience:Experts Only
Abstract / Description:Despite the importance of microRNAs (miRs) for regulation of the delicate balance between cell proliferation and death, evidence for their specific involvement during death receptor (DR)-mediated apoptosis is scarce. Transfection with miR-133b rendered resistant HeLa cells sensitive to tumor necrosis factor-alpha (TNF alpha)-induced cell death. Similarly, miR-133b caused exacerbated proapoptotic responses to TNF-related apoptosis-inducing ligand (TRAIL) or an activating antibody to Fas/CD95. Comprehensive analysis, encompassing global RNA or protein expression profiling performed by microarray experiments and pulsed stable isotope labeling with amino acids in cell culture (pSILAC), led to the discovery of the antiapoptotic protein Fas apoptosis inhibitory molecule (FAIM) as immediate miR-133b target. Moreover, miR-133b impaired the expression of the detoxifying protein glutathione-S-transferase pi (GSTP1). Expression of miR-133b in tumor specimens of prostate cancer patients was significantly downregulated in 75% of the cases, when compared with matched healthy tissue. Furthermore, introduction of synthetic miR-133b into an ex-vivo model of prostate cancer resulted in impaired proliferation and cellular metabolic activity. PC3 cells were also sensitized to apoptotic stimuli after transfection with miR-133b similar to HeLa cells. These data reveal the ability of a single miR to influence major apoptosis pathways, suggesting an essential role for this molecule during cellular transformation, tumorigenesis and tissue homeostasis.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:Beate Löhr
Affiliations:MPI für Infektionsbiologie/Department of Immunology
MPI für Infektionsbiologie/Core Facilities
External Affiliations:AF, CS: Charite, Dept Urol, D-13353 Berlin, Germany; AF, KJ: Berlin Inst Urol Res, Berlin, Germany; AF: Free Univ Berlin, Dept Biol Chem & Pharm, Berlin, Germany; MOA: Univ Oslo, Biotechnol Ctr Oslo, Oslo, Norway; MOA: Univ Oslo, Rikshosp, Prote Core Facil, N-0027 Oslo, Norway; MOA: Norwegian Univ Life Sci, Prote Core Facil, As, Norway
Identifiers:ISI:000305339200058 [ID No:1]
ISSN:1932-6203 [ID No:2]
DOI:10.1371/journal.pone.0035345 [ID No:3]
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