%0 Journal Article
%T Interferon-¦Ã-induced activation of Signal Transducer and Activator of Transcription 1 (STAT1) up-regulates the tumor suppressing microRNA-29 family in melanoma cells
%A Martina J Schmitt
%A Demetra Philippidou
%A Susanne E Reinsbach
%A Christiane Margue
%A Anke Wienecke-Baldacchino
%A Dorothee Nashan
%A Iris Behrmann
%A Stephanie Kreis
%J Cell Communication and Signaling
%D 2012
%I BioMed Central
%R 10.1186/1478-811x-10-41
%X We recently described a distinct and dynamic regulation of a whole panel of microRNAs (miRNAs) after IFN-¦Ã-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-¦Ã ¡ú Jak¡ú P-STAT1 ¡ú miR-29 ¡ú miR-29 target genes and its implication for melanoma growth.Here we show that IFN-¦Ã 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-¦Ã-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.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.In the past decade, small non-coding microRNAs (miRNAs) have been identified as new and important players in post-transcriptional gene regulation and ever since, their expression patterns and cellular functions have been investigated in cancer and other diseases [1,2]. MiRNA biogenesis can be differentially regulated [3], but generally starts with the generation of a primary (pri-) miRNA transcript (several thousand nucleotides long), which is subsequently processed into a 70¨C80 nuc
%K IFN-¦Ã
%K Jak/STAT pathway
%K STAT1
%K Signaling
%K Melanoma
%K miR-29
%K Tumor-suppressor
%U http://www.biosignaling.com/content/10/1/41