Effect of miR-21 and miR-30b/c on TRAIL-induced apoptosis in glioma cells

C. Quintavalle, E. Donnarumma, M. Iaboni, G. Roscigno, M. Garofalo, G. Romano, D. Fiore, P. De Marinis, C. M. Croce, G. Condorelli

Research output: Contribution to journalArticle

Abstract

Glioblastoma is the most frequent brain tumor in adults and is the most lethal form of human cancer. Despite the improvements in treatments, survival of patients remains poor. To define novel pathways that regulate susceptibility to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in glioma, we have performed genome-wide expression profiling of microRNAs (miRs). We show that in TRAIL-resistant glioma cells, levels of different miRs are increased, and in particular, miR-30b/c and-21. We demonstrate that these miRs impair TRAIL-dependent apoptosis by inhibiting the expression of key functional proteins. T98G-sensitive cells treated with miR-21 or-30b/c become resistant to TRAIL. Furthermore, we demonstrate that miR-30b/c and miR-21 target respectively the 3′ untranslated region of caspase-3 and TAp63 mRNAs, and that those proteins mediate some of the effects of miR-30 and-21 on TRAIL resistance, even in human glioblastoma primary cells and in lung cancer cells. In conclusion, we show that high expression levels of miR-21 and-30b/c are needed to maintain the TRAIL-resistant phenotype, thus making these miRs as promising therapeutic targets for TRAIL resistance in glioma.

Original languageEnglish
Pages (from-to)4001-4008
Number of pages8
JournalOncogene
Volume32
Issue number34
DOIs
Publication statusPublished - Aug 22 2013

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Keywords

  • Apoptosis
  • Glioblastoma
  • MicroRNA
  • Therapy
  • TRAIL
  • Treatment

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Quintavalle, C., Donnarumma, E., Iaboni, M., Roscigno, G., Garofalo, M., Romano, G., Fiore, D., De Marinis, P., Croce, C. M., & Condorelli, G. (2013). Effect of miR-21 and miR-30b/c on TRAIL-induced apoptosis in glioma cells. Oncogene, 32(34), 4001-4008. https://doi.org/10.1038/onc.2012.410