Journal
PLOS ONE
Volume 7, Issue 10, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0046990
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Funding
- Swedish Research Council [523-2009-3517, 521-2010-3518]
- Ake Olsson's Foundation for Haematological Research
- Swedish Cancer Foundation
- Ake Wiberg's Foundation
- King Gustaf V Jubilee Fund
- Cancer Society in Stockholm
- Axel and Signe Lagerman's Donation Foundation
- Karolinska Institutet
- Stockholm County Council
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MicroRNAs (miRNAs) are short non-coding RNA regulators that control gene expression mainly through post-transcriptional silencing. We previously identified miR-205 in a signature for human cervical cancer using a deep sequencing approach. In this study, we confirmed that miR-205 expression was frequently higher in human cervical cancer than their matched normal tissue samples. Functionally, we demonstrate that miR-205 promotes cell proliferation and migration in human cervical cancer cells. To further understand the biological roles of miR-205, we performed in vivo crosslinking and Argonaute 2 immunoprecipitation of miRNA ribonucleoprotein complexes followed by microarray analysis (CLIP-Chip) to identify its potential mRNA targets. Applying CLIP-Chip on gain- and loss-of-function experiments, we identified a set of transcripts as potential targets of miR-205. Several targets are functionally involved in cellular proliferation and migration. Two of them, CYR61 and CTGF, were further validated by Western blot analysis and quantification of mRNA enrichment in the Ago2 immunoprecipitates using qRT-PCR. Furthermore, both CYR61 and CTGF were downregulated in cervical cancer tissues. In summary, our findings reveal novel functional roles and targets of miR-205 in human cervical cancer, which may provide new insights about its role in cervical carcinogenesis and its potential value for clinical diagnosis.
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