MicroRNA-29b-1 impairs in vitro cell proliferation, self‑renewal and chemoresistance of human osteosarcoma 3AB-OS cancer stem cells

  • Authors:
    • Riccardo Di Fiore
    • Rosa Drago-Ferrante
    • Francesca Pentimalli
    • Domenico Di Marzo
    • Iris Maria Forte
    • Antonella D'Anneo
    • Daniela Carlisi
    • Anna De Blasio
    • Michela Giuliano
    • Giovanni Tesoriere
    • Antonio Giordano
    • Renza Vento
  • View Affiliations

  • Published online on: August 22, 2014     https://doi.org/10.3892/ijo.2014.2618
  • Pages: 2013-2023
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Abstract

Osteosarcoma (OS) is the most common type of bone cancer, with a peak incidence in the early childhood. Emerging evidence suggests that treatments targeting cancer stem cells (CSCs) within a tumor can halt cancer and improve patient survival. MicroRNAs (miRNAs) have been implicated in the maintenance of the CSC phenotype, thus, identification of CSC-related miRNAs would provide information for a better understanding of CSCs. Downregulation of miRNA-29 family members (miR-29a/b/c; miR‑29s) was observed in human OS, however, little is known about the functions of miR-29s in human OS CSCs. Previously, during the characterization of 3AB-OS cells, a CSC line selected from human OS MG63 cells, we showed a potent downregulation of miR-29b. In this study, after stable transfection of 3AB-OS cells with miR-29b-1, we investigated the role of miR-29b-1 in regulating cell proliferation, sarcosphere-forming ability, clonogenic growth, chemosensitivity, migration and invasive ability of 3AB-OS cells, in vitro. We found that, miR-29b-1 overexpression consistently reduced both, 3AB-OS CSCs growth in two- and three-dimensional culture systems and their sarcosphere- and colony-forming ability. In addition, while miR-29b-1 overexpression sensitized 3AB-OS cells to chemotherapeutic drug-induced apoptosis, it did not influence their migratory and invasive capacities, thus suggesting a context-depending role of miR-29b-1. Using publicly available databases, we proceeded to identify potential miR-29b target genes, known to play a role in the above reported functions. Among these targets we analyzed CD133, N-Myc, CCND2, E2F1 and E2F2, Bcl-2 and IAP-2. We also analyzed the most important stemness markers as Oct3/4, Sox2 and Nanog. Real-time RT-PCR and western-blot analyses showed that miR-29b-1 negatively regulated the expression of these markers. Overall, the results show that miR-29b-1 suppresses stemness properties of 3AB-OS CSCs and suggest that developing miR-29b-1 as a novel therapeutic agent might offer benefits for OS treatment.
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November-2014
Volume 45 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Di Fiore R, Drago-Ferrante R, Pentimalli F, Di Marzo D, Forte IM, D'Anneo A, Carlisi D, De Blasio A, Giuliano M, Tesoriere G, Tesoriere G, et al: MicroRNA-29b-1 impairs in vitro cell proliferation, self‑renewal and chemoresistance of human osteosarcoma 3AB-OS cancer stem cells. Int J Oncol 45: 2013-2023, 2014
APA
Di Fiore, R., Drago-Ferrante, R., Pentimalli, F., Di Marzo, D., Forte, I.M., D'Anneo, A. ... Vento, R. (2014). MicroRNA-29b-1 impairs in vitro cell proliferation, self‑renewal and chemoresistance of human osteosarcoma 3AB-OS cancer stem cells. International Journal of Oncology, 45, 2013-2023. https://doi.org/10.3892/ijo.2014.2618
MLA
Di Fiore, R., Drago-Ferrante, R., Pentimalli, F., Di Marzo, D., Forte, I. M., D'Anneo, A., Carlisi, D., De Blasio, A., Giuliano, M., Tesoriere, G., Giordano, A., Vento, R."MicroRNA-29b-1 impairs in vitro cell proliferation, self‑renewal and chemoresistance of human osteosarcoma 3AB-OS cancer stem cells". International Journal of Oncology 45.5 (2014): 2013-2023.
Chicago
Di Fiore, R., Drago-Ferrante, R., Pentimalli, F., Di Marzo, D., Forte, I. M., D'Anneo, A., Carlisi, D., De Blasio, A., Giuliano, M., Tesoriere, G., Giordano, A., Vento, R."MicroRNA-29b-1 impairs in vitro cell proliferation, self‑renewal and chemoresistance of human osteosarcoma 3AB-OS cancer stem cells". International Journal of Oncology 45, no. 5 (2014): 2013-2023. https://doi.org/10.3892/ijo.2014.2618