Role of the Long Non-Coding RNA Growth Arrest-Specific 5 in Glucocorticoid Response in Children with Inflammatory Bowel Disease

Marianna Lucafò, Alessia Di Silvestre, Maurizio Romano, Alice Avian, Roberta Antonelli, Stefano Martelossi, Samuele Naviglio, Alberto Tommasini, Gabriele Stocco, Alessandro Ventura, Giuliana Decorti, Sara De Iudicibus

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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, we 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, to confirm the sensitivity and specificity of these lncRNAs. 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 we found that GAS5 knock-down reduced the proliferation during GC treatment. Furthermore, for the first time, we measured GAS5 levels in 19 paediatric IBD patients at diagnosis and after the first cycle of GCs, and we demonstrated an up-regulation of the lncRNA in patients with unfavourable steroid response. Our preliminary results indicate that GAS5 could be considered a novel pharmacogenomic marker useful for the personalization of GC therapy.

Original languageEnglish
Pages (from-to)87-93
Number of pages7
JournalBasic and Clinical Pharmacology and Toxicology
Volume122
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

Fingerprint

Long Noncoding RNA
Inflammatory Bowel Diseases
Glucocorticoids
Growth
Pediatrics
Steroids
Therapeutics
Pharmacogenetics
Ovarian Neoplasms
Colonic Neoplasms
Autoimmune Diseases
Cytoplasm
Up-Regulation
Cells
Sensitivity and Specificity
Cell Line
Incidence

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Cite this

Role of the Long Non-Coding RNA Growth Arrest-Specific 5 in Glucocorticoid Response in Children with Inflammatory Bowel Disease. / 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.

In: Basic and Clinical Pharmacology and Toxicology, Vol. 122, No. 1, 01.01.2018, p. 87-93.

Research output: Contribution to journalArticle

@article{9d84bdf9144244c9a51147d59219f300,
title = "Role of the Long Non-Coding RNA Growth Arrest-Specific 5 in Glucocorticoid Response in Children with Inflammatory Bowel Disease",
abstract = "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, we 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, to confirm the sensitivity and specificity of these lncRNAs. 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 we found that GAS5 knock-down reduced the proliferation during GC treatment. Furthermore, for the first time, we measured GAS5 levels in 19 paediatric IBD patients at diagnosis and after the first cycle of GCs, and we demonstrated an up-regulation of the lncRNA in patients with unfavourable steroid response. Our preliminary results indicate that GAS5 could be considered a novel pharmacogenomic marker useful for the personalization of GC therapy.",
author = "Marianna Lucaf{\`o} and {Di Silvestre}, Alessia and Maurizio Romano and Alice Avian and Roberta Antonelli and Stefano Martelossi and Samuele Naviglio and Alberto Tommasini and Gabriele Stocco and Alessandro Ventura and Giuliana Decorti and {De Iudicibus}, Sara",
year = "2018",
month = "1",
day = "1",
doi = "10.1111/bcpt.12851",
language = "English",
volume = "122",
pages = "87--93",
journal = "Basic and Clinical Pharmacology and Toxicology",
issn = "1742-7835",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Role of the Long Non-Coding RNA Growth Arrest-Specific 5 in Glucocorticoid Response in Children with Inflammatory Bowel Disease

AU - Lucafò, Marianna

AU - Di Silvestre, Alessia

AU - Romano, Maurizio

AU - Avian, Alice

AU - Antonelli, Roberta

AU - Martelossi, Stefano

AU - Naviglio, Samuele

AU - Tommasini, Alberto

AU - Stocco, Gabriele

AU - Ventura, Alessandro

AU - Decorti, Giuliana

AU - De Iudicibus, Sara

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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, we 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, to confirm the sensitivity and specificity of these lncRNAs. 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 we found that GAS5 knock-down reduced the proliferation during GC treatment. Furthermore, for the first time, we measured GAS5 levels in 19 paediatric IBD patients at diagnosis and after the first cycle of GCs, and we demonstrated an up-regulation of the lncRNA in patients with unfavourable steroid response. Our preliminary results indicate that GAS5 could be considered a novel pharmacogenomic marker useful for the personalization of GC therapy.

AB - 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, we 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, to confirm the sensitivity and specificity of these lncRNAs. 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 we found that GAS5 knock-down reduced the proliferation during GC treatment. Furthermore, for the first time, we measured GAS5 levels in 19 paediatric IBD patients at diagnosis and after the first cycle of GCs, and we demonstrated an up-regulation of the lncRNA in patients with unfavourable steroid response. Our preliminary results indicate that GAS5 could be considered a novel pharmacogenomic marker useful for the personalization of GC therapy.

UR - http://www.scopus.com/inward/record.url?scp=85038832423&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85038832423&partnerID=8YFLogxK

U2 - 10.1111/bcpt.12851

DO - 10.1111/bcpt.12851

M3 - Article

AN - SCOPUS:85038832423

VL - 122

SP - 87

EP - 93

JO - Basic and Clinical Pharmacology and Toxicology

JF - Basic and Clinical Pharmacology and Toxicology

SN - 1742-7835

IS - 1

ER -