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Journal Article

MiR-133b Targets Antiapoptotic Genes and Enhances Death Receptor-Induced Apoptosis

MPS-Authors
http://pubman.mpdl.mpg.de/cone/persons/resource/persons82091

Patron,  Juan Pablo
Department of Immunology, Max Planck Institute for Infection Biology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons81814

Bild,  Matthias
Department of Immunology, Max Planck Institute for Infection Biology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons81960

Jung,  Ulrike
Department of Immunology, Max Planck Institute for Infection Biology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons82064

Müller,  Henrik
Department of Immunology, Max Planck Institute for Infection Biology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons82096

Piso,  Chloe
Department of Immunology, Max Planck Institute for Infection Biology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons82058

Mollenkopf,  Hans-Joachim
Core Facilities / Microarray, Max Planck Institute for Infection Biology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons81969

Kaufmann,  Stefan H. E.
Department of Immunology, Max Planck Institute for Infection Biology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons82146

Schreiber,  Joerg
Department of Immunology, Max Planck Institute for Infection Biology, Max Planck Society;

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Fulltext (public)

PLoS_One_2012_7_e35345.pdf
(Publisher version), 2MB

Supplementary Material (public)
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Citation

Patron, J. P., Fendler, A., Bild, M., Jung, U., Müller, H., Arntzen, M. O., et al. (2012). MiR-133b Targets Antiapoptotic Genes and Enhances Death Receptor-Induced Apoptosis. PLoS ONE, 7(4): e35345. doi:10.1371/journal.pone.0035345.


Cite as: http://hdl.handle.net/11858/00-001M-0000-000E-BDFB-B
Abstract
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.