Article (Scientific journals)
New Target Genes of MITF-Induced microRNA-211 Contribute to Melanoma Cell Invasion
Margue, Christiane; Philippidou, Demetra; Reinsbach, Susanne et al.
2013In PLoS ONE, 8 (9)
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Abstract :
[en] The non-coding microRNAs (miRNA) have tissue- and disease-specific expression patterns. They down-regulate target mRNAs, which likely impacts on most fundamental cellular processes. Differential expression patterns of miRNAs are currently being exploited for identification of biomarkers for early disease diagnosis, prediction of progression for melanoma and other cancers and as promising drug targets, since they can easily be inhibited or replaced in a given cellular context. Before successfully manipulating miRNAs in clinical settings, their precise expression levels, endogenous functions and thus their target genes have to be determined. MiR-211, a melanocyte lineage-specific small non-coding miRNA, is located in an intron of TRPM1, a target gene of the microphtalmia-associated transcription factor (MITF). By transcriptionally up-regulating TRPM1, MITF, which is critical for both melanocyte differentiation and survival and for melanoma progression, indirectly drives the expression of miR-211. Expression of this miRNA is often reduced in melanoma samples. Here, we investigated functional roles of miR-211 by identifying and studying new target genes. We show that MITF-correlated miR-211 expression levels are mostly but not always reduced in a panel of 11 melanoma cell lines and in primary and metastatic melanoma compared to normal melanocytes and nevi, respectively. MiR-211 itself only marginally impacted on cell invasion and migration, while perturbation of some new miR-211 target genes, such as AP1S2, SOX11, IGFBP5, and SERINC3 significantly increased invasion. These results and the variable expression levels of miR-211 raise serious doubts on the value of miR-211 as a melanoma tumor-suppressing miRNA and/or as a biomarker for melanoma.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Margue, Christiane  ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
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
Schmitt, Martina ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
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 :
no
Language :
English
Title :
New Target Genes of MITF-Induced microRNA-211 Contribute to Melanoma Cell Invasion
Publication date :
05 September 2013
Journal title :
PLoS ONE
ISSN :
1932-6203
Publisher :
Public Library of Science, San Franscisco, United States - California
Volume :
8
Issue :
9
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
Funders :
This study was funded by a research grant from the University of Luxembourg (F1R_LSC-PUL-09MIRN). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Available on ORBilu :
since 10 October 2013

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