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Role of the Long Non‐Coding RNA Growth Arrest‐Specific 5 in Glucocorticoid Response in Children with Inflammatory Bowel Disease
Author(s) -
Lucafò Marianna,
Di Silvestre Alessia,
Romano Maurizio,
Avian Alice,
Antonelli Roberta,
Martelossi Stefano,
Naviglio Samuele,
Tommasini Alberto,
Stocco Gabriele,
Ventura Alessandro,
Decorti Giuliana,
De Iudicibus Sara
Publication year - 2018
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12851
Subject(s) - gas5 , inflammatory bowel disease , long non coding rna , medicine , gene silencing , glucocorticoid , pharmacogenomics , disease , autophagy , cancer research , immunology , biology , pharmacology , downregulation and upregulation , apoptosis , gene , genetics
Abstract Glucocorticoids ( GC s) are widely employed in inflammatory, autoimmune and neoplastic diseases, and, despite the introduction of novel therapies, remain the first‐line treatment for inducing remission in inflammatory bowel disease ( IBD ). Given the high incidence of suboptimal response, associated with a significant number of side‐effects, that are particularly severe in paediatric patients, the identification of subjects that are most likely to respond poorly to GC s is extremely important. Recent evidence suggests that the long non‐coding RNA (lnc RNA ) GAS 5 could be a potential marker of GC resistance. To address this issue, we evaluated the association between the lnc RNA GAS 5 and the efficacy of steroids, in terms of inhibition of proliferation, in two cell lines derived from colon and ovarian cancers, to confirm the sensitivity and specificity of these lnc RNA s. These cells showed a different sensitivity to GC s and revealed differential expression of GAS 5 after treatment. GAS 5 was up‐regulated in GC ‐resistant cells and accumulated more in the cytoplasm compared to the nucleus in response to the drug. The functions of GAS 5 were assessed by silencing, and we found that GAS 5 knock‐down reduced the proliferation during GC treatment. Furthermore, for the first time, we measured GAS 5 levels in 19 paediatric IBD patients at diagnosis and after the first cycle of GC s, and we demonstrated an up‐regulation of the lnc RNA in patients with unfavourable steroid response. Our preliminary results indicate that GAS 5 could be considered a novel pharmacogenomic marker useful for the personalization of GC therapy.