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- aggregation classification "A1".
- aggregation creator B223766.
- aggregation creator B223767.
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- aggregation creator person.
- aggregation creator person.
- aggregation creator person.
- aggregation date "2011".
- aggregation format "application/pdf".
- aggregation hasFormat 2123760.bibtex.
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- aggregation isPartOf urn:issn:0950-9232.
- aggregation language "eng".
- aggregation rights "I have transferred the copyright for this publication to the publisher".
- aggregation subject "Medicine and Health Sciences".
- aggregation title "Hsa-mir-145 is the top EWS-FLI1-repressed microRNA involved in a positive feedback loop in Ewing's sarcoma".
- aggregation abstract "EWS-FLI1 is a chromosome translocation-derived chimeric transcription factor that has a central and rate-limiting role in the pathogenesis of Ewing's sarcoma. Although the EWS-FLI1 transcriptomic signature has been extensively characterized on the mRNA level, information on its impact on non-coding RNA expression is lacking. We have performed a genome-wide analysis of microRNAs affected by RNAi-mediated silencing of EWS-FLI1 in Ewing's sarcoma cell lines, and differentially expressed between primary Ewing's sarcoma and mesenchymal progenitor cells. Here, we report on the identification of hsa-mir-145 as the top EWS-FLI1-repressed microRNA. Upon knockdown of EWS-FLI1, hsa-mir-145 expression dramatically increases in all Ewing's sarcoma cell lines tested. Vice versa, ectopic expression of the microRNA in Ewing's sarcoma cell lines strongly reduced EWS-FLI1 protein, whereas transfection of an anti-mir to hsa-mir-145 increased the EWS-FLI1 levels. Reporter gene assays revealed that this modulation of EWS-FLI1 protein was mediated by the microRNA targeting the FLI1 3'-untranslated region. Mutual regulations of EWS-FLI1 and hsa-mir-145 were mirrored by an inverse correlation between their expression levels in four of the Ewing's sarcoma cell lines tested. Consistent with the role of EWS-FLI1 in Ewing's sarcoma growth regulation, forced hsa-mir-145 expression halted Ewing's sarcoma cell line growth. These results identify feedback regulation between EWS-FLI1 and hsa-mir-145 as an important component of the EWS-FLI1-mediated Ewing's sarcomagenesis that may open a new avenue to future microRNA-mediated therapy of this devastating malignant disease.".
- aggregation authorList BK489992.
- aggregation endPage "2180".
- aggregation issue "18".
- aggregation startPage "2173".
- aggregation volume "30".
- aggregation aggregates 3147242.
- aggregation isDescribedBy 2123760.
- aggregation similarTo onc.2010.581.
- aggregation similarTo LU-2123760.