Abstract
Glucocorticoids (GCs) exert their effects through regulation of gene expression after activation in the cytoplasm of the glucocorticoid receptor (GR) encoded by NR3C1 gene. A negative feedback mechanism resulting in GR autoregulation has been demonstrated through the binding of the activated receptor to intragenic sequences called GRE-like elements, contained in GR gene.
The long noncoding RNA growth arrest–specific transcript 5 (GAS5) interacts with the activated GR suppressing its transcriptional activity. The aim of this study was to evaluate the possible role of GAS5 and NR3C1 gene expression in the antiproliferative effect of methylprednisolone in peripheral blood mononuclear cells and to correlate the expression with individual sensitivity to GCs. Subjects being poor responders to GCs presented higher levels of GAS5 and NR3C1 in comparison with good responders. We suggest that abnormal levels of GAS5 may alter GC effectiveness, probably interfering with the mechanism of GR autoregulation.
Keywords: GAS5, gene expression, glucocorticoid receptor, long noncoding RNA, methylprednisolone, NR3C1 gene, proliferation assay.
Current Molecular Medicine
Title:Long Noncoding RNA GAS5: A Novel Marker Involved in Glucocorticoid Response
Volume: 15 Issue: 1
Author(s): M. Lucafo, S. De Iudicibus, A. Di Silvestre, M. Pelin, L. Candussio, S. Martelossi, A. Tommasini, E. Piscianz, A. Ventura and G. Decorti
Affiliation:
Keywords: GAS5, gene expression, glucocorticoid receptor, long noncoding RNA, methylprednisolone, NR3C1 gene, proliferation assay.
Abstract: Glucocorticoids (GCs) exert their effects through regulation of gene expression after activation in the cytoplasm of the glucocorticoid receptor (GR) encoded by NR3C1 gene. A negative feedback mechanism resulting in GR autoregulation has been demonstrated through the binding of the activated receptor to intragenic sequences called GRE-like elements, contained in GR gene.
The long noncoding RNA growth arrest–specific transcript 5 (GAS5) interacts with the activated GR suppressing its transcriptional activity. The aim of this study was to evaluate the possible role of GAS5 and NR3C1 gene expression in the antiproliferative effect of methylprednisolone in peripheral blood mononuclear cells and to correlate the expression with individual sensitivity to GCs. Subjects being poor responders to GCs presented higher levels of GAS5 and NR3C1 in comparison with good responders. We suggest that abnormal levels of GAS5 may alter GC effectiveness, probably interfering with the mechanism of GR autoregulation.
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Lucafo M., Iudicibus De S., Silvestre Di A., Pelin M., Candussio L., Martelossi S., Tommasini A., Piscianz E., Ventura A. and Decorti G., Long Noncoding RNA GAS5: A Novel Marker Involved in Glucocorticoid Response, Current Molecular Medicine 2015; 15 (1) . https://dx.doi.org/10.2174/1566524015666150114122354
DOI https://dx.doi.org/10.2174/1566524015666150114122354 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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