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Differential expression of GAS 5 in rapamycin‐induced reversion of glucocorticoid resistance
Author(s) -
Lucafò Marianna,
Bravin Vanessa,
Tommasini Alberto,
Martelossi Stefano,
Rabach Ingrid,
Ventura Alessandro,
Decorti Giuliana,
De Iudicibus Sara
Publication year - 2016
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12572
Subject(s) - glucocorticoid , peripheral blood mononuclear cell , taqman , downregulation and upregulation , biomarker , methylprednisolone , chemistry , cancer research , pharmacology , biology , real time polymerase chain reaction , medicine , immunology , in vitro , gene , biochemistry
Summary This study evaluates the association between the long noncoding RNA GAS 5 levels and the anti‐proliferative effect of the glucocorticoid ( GC ) methylprednisolone ( MP ) alone and in combination with rapamycin in peripheral blood mononuclear cells ( PBMC s) 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 GAS 5 gene were evaluated by real‐time RT ‐ PCR TaqMan analysis. We confirmed a role for GAS 5 in modulating GC response: poor responders presented higher levels of GAS 5 in comparison with good responders. Interestingly, when PBMC s were treated with the combination of rapamycin plus MP , the high levels of GAS 5 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). GAS 5 is involved in GC resistance and co‐treatment of rapamycin with GC s restores GC effectiveness in poor responders through the downregulation of the long noncoding RNA . GAS 5 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.