Differential expression of GAS5 in rapamycin-induced reversion of glucocorticoid resistance

Marianna Lucafò, Vanessa Bravin, Alberto Tommasini, Stefano Martelossi, Ingrid Rabach, Alessandro Ventura, Giuliana Decorti, Sara De Iudicibus

Research output: Contribution to journalArticlepeer-review

Abstract

This study evaluates the association between the long noncoding RNA GAS5 levels and the anti-proliferative effect of the glucocorticoid (GC) methylprednisolone (MP) alone and in combination with rapamycin in peripheral blood mononuclear cells (PBMCs) obtained from healthy donors. The effect of MP, rapamycin, and MP plus rapamycin was determined in 17 healthy donors by labelling metabolically active cells with [methyl-3H] thymidine and the expression levels of GAS5 gene were evaluated by real-time RT-PCR TaqMan analysis. We confirmed a role for GAS5 in modulating GC response: poor responders presented higher levels of GAS5 in comparison with good responders. Interestingly, when PBMCs were treated with the combination of rapamycin plus MP, the high levels of GAS5 observed for each drug in the MP poor responders group decreased in comparison with rapamycin (P value = 0.0134) or MP alone (P value = 0.0193). GAS5 is involved in GC resistance and co-treatment of rapamycin with GCs restores GC effectiveness in poor responders through the downregulation of the long noncoding RNA. GAS5 could be considered a biomarker to personalize therapy and a novel therapeutic target useful for the development of new pharmacological approaches to restore GC sensitivity.

Original languageEnglish
Pages (from-to)602-605
Number of pages4
JournalClinical and Experimental Pharmacology and Physiology
Volume43
Issue number6
DOIs
Publication statusPublished - Jun 1 2016

Keywords

  • GAS5
  • Glucocorticoids
  • Long noncoding RNA
  • Methylprednisolone
  • Rapamycin

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Pharmacology

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