lncRNA GAS5 and the efficacy of steroids

Glucocorticoids (GCs) 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 GCs is extremely important. Recent evidence suggests that the long non-coding RNA (lncRNA) GAS5 could be a potential marker of GC resistance.

To address this issue, researchers from the University of Trieste evaluated the association between the lncRNA GAS5 and the efficacy of steroids, in terms of inhibition of proliferation, in two cell lines derived from colon and ovarian cancers, in order to confirm the sensitivity and specificity of these lncRNA. These cells showed a different sensitivity to GCs, and revealed differential expression of GAS5 after treatment. GAS5 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 GAS5 were assessed by silencing, and the researchers found that GAS5 knockdown reduced the proliferation during GC treatment. Furthermore, for the first time, they measured GAS5 levels in 19 paediatric IBD patients at diagnosis and after the first cycle of GCs, and they demonstrated an up-regultation of the lncRNA in patients with unfavourable steroid response. These preliminary results indicate that GAS5 could be considered a novel pharmacogenomic marker useful for the personalization of GC therapy.

Lucafò M, Di Silvestre A, Romano M, Avian A, Antonelli R, Martelossi S, Naviglio S, Tommasini A, Stocco G, Ventura A, Giuliana Decorti MD, De Iudicibus S. (2017) Role of the Long Non-Coding RNA GAS5 in Glucocorticoid Response in Children with Inflammatory Bowel Disease. Basic Clin Pharmacol Toxicol [Epub ahead of print]. [abstract]

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