Advanced search
1 file | 502.31 KB Add to list

Hsa-mir-145 is the top EWS-FLI1-repressed microRNA involved in a positive feedback loop in Ewing's sarcoma

(2011) ONCOGENE. 30(18). p.2173-2180
Author
Organization
Project
Bioinformatics: from nucleotids to networks (N2N)
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.
Keywords
mir-145, EWS-FLI1, microRNA, Ewing's sarcoma, CELL-GROWTH, STEM-CELLS, IN-VITRO, MIR-145, EWS-FLI1, P53, EXPRESSION, CANCER, DIFFERENTIATION, SIGNATURE

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 502.31 KB

Citation

Please use this url to cite or link to this publication:

MLA
Ban, J, G Jug, Pieter Mestdagh, et al. “Hsa-mir-145 Is the Top EWS-FLI1-repressed microRNA Involved in a Positive Feedback Loop in Ewing’s Sarcoma.” ONCOGENE 30.18 (2011): 2173–2180. Print.
APA
Ban, J., Jug, G., Mestdagh, P., Schwentner, R., Kauer, M., Aryee, D., Schaefer, K.-L., et al. (2011). Hsa-mir-145 is the top EWS-FLI1-repressed microRNA involved in a positive feedback loop in Ewing’s sarcoma. ONCOGENE, 30(18), 2173–2180.
Chicago author-date
Ban, J, G Jug, Pieter Mestdagh, R Schwentner, M Kauer, DNT Aryee, K-L Schaefer, et al. 2011. “Hsa-mir-145 Is the Top EWS-FLI1-repressed microRNA Involved in a Positive Feedback Loop in Ewing’s Sarcoma.” Oncogene 30 (18): 2173–2180.
Chicago author-date (all authors)
Ban, J, G Jug, Pieter Mestdagh, R Schwentner, M Kauer, DNT Aryee, K-L Schaefer, F Nakatani, K Scotlandi, M Reiter, D Strunk, Franki Speleman, Jo Vandesompele, and H Kovar. 2011. “Hsa-mir-145 Is the Top EWS-FLI1-repressed microRNA Involved in a Positive Feedback Loop in Ewing’s Sarcoma.” Oncogene 30 (18): 2173–2180.
Vancouver
1.
Ban J, Jug G, Mestdagh P, Schwentner R, Kauer M, Aryee D, et al. Hsa-mir-145 is the top EWS-FLI1-repressed microRNA involved in a positive feedback loop in Ewing’s sarcoma. ONCOGENE. 2011;30(18):2173–80.
IEEE
[1]
J. Ban et al., “Hsa-mir-145 is the top EWS-FLI1-repressed microRNA involved in a positive feedback loop in Ewing’s sarcoma,” ONCOGENE, vol. 30, no. 18, pp. 2173–2180, 2011.
@article{2123760,
  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.},
  author       = {Ban, J and Jug, G and Mestdagh, Pieter and Schwentner, R and Kauer, M and Aryee, DNT and Schaefer, K-L and Nakatani, F and Scotlandi, K and Reiter, M and Strunk, D and Speleman, Franki and Vandesompele, Jo and Kovar, H},
  issn         = {0950-9232},
  journal      = {ONCOGENE},
  keywords     = {mir-145,EWS-FLI1,microRNA,Ewing's sarcoma,CELL-GROWTH,STEM-CELLS,IN-VITRO,MIR-145,EWS-FLI1,P53,EXPRESSION,CANCER,DIFFERENTIATION,SIGNATURE},
  language     = {eng},
  number       = {18},
  pages        = {2173--2180},
  title        = {Hsa-mir-145 is the top EWS-FLI1-repressed microRNA involved in a positive feedback loop in Ewing's sarcoma},
  url          = {http://dx.doi.org/10.1038/onc.2010.581},
  volume       = {30},
  year         = {2011},
}

Altmetric
View in Altmetric
Web of Science
Times cited: