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

Riccardo Di Fiore, Antonella D'Anneo, Michela Giuliano, Renza Vento, Anna De Blasio, Daniela Carlisi, Domenico Di Marzo, Iris Maria Forte, Francesca Pentimali, Renza Vento, Giovani Tesoriere, Antonio Giordano, Rosa Drago Ferrante

Risultato della ricerca: Articlepeer review

45 Citazioni (Scopus)

Abstract

Osteosarcoma (OS) is the most common type ofbone cancer, with a peak incidence in the early childhood.Emerging evidence suggests that treatments targeting cancerstem cells (CSCs) within a tumor can halt cancer and improvepatient survival. MicroRNAs (miRNAs) have been implicatedin the maintenance of the CSC phenotype, thus, identificationof CSC-related miRNAs would provide information for abetter understanding of CSCs. Downregulation of miRNA-29family members (miR-29a/b/c; miR‑29s) was observed inhuman OS, however, little is known about the functions ofmiR-29s in human OS CSCs. Previously, during the characterizationof 3AB-OS cells, a CSC line selected from humanOS MG63 cells, we showed a potent downregulation ofmiR-29b. In this study, after stable transfection of 3AB-OScells with miR-29b-1, we investigated the role of miR-29b-1in regulating cell proliferation, sarcosphere-forming ability,clonogenic growth, chemosensitivity, migration and invasiveability of 3AB-OS cells, in vitro. We found that, miR-29b-1overexpression consistently reduced both, 3AB-OS CSCsgrowth in two- and three-dimensional culture systems andtheir sarcosphere- and colony-forming ability. In addition, while miR-29b-1 overexpression sensitized 3AB-OS cells tochemotherapeutic drug-induced apoptosis, it did not influencetheir migratory and invasive capacities, thus suggesting acontext-depending role of miR-29b-1. Using publicly availabledatabases, we proceeded to identify potential miR-29btarget genes, known to play a role in the above reportedfunctions. Among these targets we analyzed CD133, N-Myc,CCND2, E2F1 and E2F2, Bcl-2 and IAP-2. We also analyzedthe most important stemness markers as Oct3/4, Sox2 andNanog. Real-time RT-PCR and western-blot analyses showedthat miR-29b-1 negatively regulated the expression of thesemarkers. Overall, the results show that miR-29b-1 suppressesstemness properties of 3AB-OS CSCs and suggest that developingmiR-29b-1 as a novel therapeutic agent might offerbenefits for OS treatment.
Lingua originaleEnglish
pagine (da-a)2013-2023
Numero di pagine11
RivistaInternational Journal of Oncology
Volume45
Stato di pubblicazionePublished - 2014

All Science Journal Classification (ASJC) codes

  • ???subjectarea.asjc.2700.2730???
  • ???subjectarea.asjc.1300.1306???

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