Cell Communication and Signaling | |
Interferon-γ-induced activation of Signal Transducer and Activator of Transcription 1 (STAT1) up-regulates the tumor suppressing microRNA-29 family in melanoma cells | |
Research | |
Dorothee Nashan1  Anke Wienecke-Baldacchino2  Christiane Margue3  Iris Behrmann3  Martina J Schmitt3  Susanne E Reinsbach3  Demetra Philippidou3  Stephanie Kreis3  | |
[1] Hautklinik, Klinikum Dortmund GmbH, Beurhausstraße 40, 44137, Dortmund, Germany;Life Sciences Research Unit, University of Luxembourg, 162A Avenue de la Faïencerie, L-1511, Luxembourg, Luxembourg;Signal Transduction Laboratory, University of Luxembourg, 162A Avenue de la Faïencerie, L-1511, Luxembourg, Luxembourg; | |
关键词: IFN-γ; Jak/STAT pathway; STAT1; Signaling; Melanoma; miR-29; Tumor-suppressor; | |
DOI : 10.1186/1478-811X-10-41 | |
received in 2012-10-19, accepted in 2012-11-27, 发布年份 2012 | |
来源: Springer | |
【 摘 要 】
BackgroundThe 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.ResultsHere 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.ConclusionsOur 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.
【 授权许可】
Unknown
© Schmitt et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
【 预 览 】
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