title: Differential expression of GAS5 in rapamycin-induced reversion of glucocorticoid resistance.
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.
authors.affiliation: Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Lucafò
authors.affiliation: Department of Life Sciences, University of Trieste, Trieste, Italy.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Bravin
authors.affiliation: Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Tommasini
authors.affiliation: Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Martelossi
authors.affiliation: Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.|Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Rabach
authors.affiliation: Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.|Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ventura
authors.affiliation: Department of Life Sciences, University of Trieste, Trieste, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Decorti
authors.affiliation: Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: De Iudicibus
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000096:biosynthesis* / Q000235:genetics; D020123:Sirolimus / Q000494:pharmacology*
chemical_list: C561567:GAS5 long non-coding RNA, human; D005938:Glucocorticoids; D062085:RNA, Long Noncoding; D020123:Sirolimus
keywords: GAS5; glucocorticoids; long noncoding RNA; methylprednisolone; rapamycin