Article (Scientific journals)
Interferon-γ-induced activation of Signal Transducer and Activator of Transcription 1 (STAT1) up-regulates the tumor suppressing microRNA-29 family in melanoma cells
Schmitt, Martina J.; Philippidou, Demetra; Reinsbach, Susanne et al.
2012In Cell Communication and Signaling, 10
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Keywords :
IFN-γ; Jak/STAT pathway; Melanoma; miR-29; Signaling; STAT1; Tumor-suppressor
Abstract :
[en] Background: The type-II-cytokine IFN-γ is a pivotal player in innate immune responses but also assumes functions in controlling tumor cell growth by orchestrating cellular responses against neoplastic cells. The role of IFN-γ in melanoma is not fully understood: it is a well-known growth inhibitor of melanoma cells in vitro. On the other hand, IFN-γ may also facilitate melanoma progression. While interferon-regulated genes encoding proteins have been intensively studied since decades, the contribution of miRNAs to effects mediated by interferons is an emerging area of research.We recently described a distinct and dynamic regulation of a whole panel of microRNAs (miRNAs) after IFN-γ-stimulation. The aim of this study was to analyze the transcriptional regulation of miR-29 family members in detail, identify potential interesting target genes and thus further elucidate a potential signaling pathway IFN-γ → Jak→ P-STAT1 → miR-29 → miR-29 target genes and its implication for melanoma growth. Results: Here we show that IFN-γ induces STAT1-dependently a profound up-regulation of the miR-29 primary cluster pri-29a∼b-1 in melanoma cell lines. Furthermore, expression levels of pri-29a∼b-1 and mature miR-29a and miR-29b were elevated while the pri-29b-2∼c cluster was almost undetectable. We observed an inverse correlation between miR-29a/b expression and the proliferation rate of various melanoma cell lines. This finding could be corroborated in cells transfected with either miR-29 mimics or inhibitors. The IFN-γ-induced G1-arrest of melanoma cells involves down-regulation of CDK6, which we proved to be a direct target of miR-29 in these cells. Compared to nevi and normal skin, and metastatic melanoma samples, miR-29a and miR-29b levels were found strikingly elevated in certain patient samples derived from primary melanoma. Conclusions: Our findings reveal that the miR-29a/b1 cluster is to be included in the group of IFN- and STAT-regulated genes. The up-regulated miR-29 family members may act as effectors of cytokine signalling in melanoma and other cancer cells as well as in the immune system. © 2012 Schmitt et al.; licensee BioMed Central Ltd.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Schmitt, Martina J.;  University of Luxembourg > Signal Transduction Laboratory
Philippidou, Demetra ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Reinsbach, Susanne ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Margue, Christiane  ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Wienecke-Baldacchino, Anke ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Nashan, Dorothee;  Hautklinik, Klinikum Dortmund GmbH
Behrmann, Iris ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Kreis, Stephanie ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
External co-authors :
yes
Language :
English
Title :
Interferon-γ-induced activation of Signal Transducer and Activator of Transcription 1 (STAT1) up-regulates the tumor suppressing microRNA-29 family in melanoma cells
Publication date :
2012
Journal title :
Cell Communication and Signaling
ISSN :
1478-811X
Publisher :
BioMed Central
Volume :
10
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
Commentary :
41 cited By (since 1996)4 Scopus
Available on ORBilu :
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