Journal Article

The long non-coding RNA GAS5 contributes to the suppression of inflammatory responses by inhibiting NF-κB activity

Pavlovic, Sonja, Stankovic, Biljana, Gasic, Vladimir, Pugnetti, Letizia, Kotur, Nikola, Lucafò, Marianna, Curci, Debora, Romano, Maurizio, Zukic, Branka, Decorti, Giuliana, Stocco, Gabriele

2024

Overview

Nuclear factor kappa B (NF-κB) is a key regulator of immune and inflammatory responses. Glucocorticoid drugs (GC) act through the glucocorticoid receptor (GR) as immunosuppressant also in pediatric patients inhibiting NF-κB activity. The long non-coding RNA GAS5 interacts with the GR, influencing GC activity. No data on the role of GAS5 on GR-dependent inhibition of NF-κB activity have been published. This study investigated the impact of GAS5 on NF-κB activity in HeLa cells overexpressing GAS5, both under basal conditions and during GC treatment. The study used EMSA, RNA-immunoprecipitation (RIP), Western blotting, and bioinformatic analyses to assess NF-κB DNA binding, GAS5-p65 interaction, and NF-κB signaling pathway modulation. GAS5 overexpression increased NF-κB DNA binding activity in untreated cells. RNA-IP confirmed a direct interaction between GAS5 and the NF-κB subunit p65, suggesting a potential regulatory mechanism. GAS5 overexpression led to downregulation of NF-κB target genes, TNF-α, and NR3C1. GC treatment reduced NF-κB DNA binding activity in GAS5-overexpressing cells, indicating a potential synergistic effect. Furthermore, GAS5 overexpression increased IκB levels and reduced p-p65/pan-p65 levels during GC treatment. GAS5 appears to modulate NF-κB activity in a complex manner, influencing both basal and GC-induced signaling. The interaction between GAS5, GCs, and NF-κB is multi-faceted, and further research is needed to fully elucidate the underlying mechanisms. These findings suggest that GAS5 could be a potential target for personalized therapy, particularly in pediatric patients with inflammatory conditions.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Cancer / Deoxyribonucleic acid / DNA / Down-regulation / Gas5 / Gene expression / Glucocorticoid receptors / Glucocorticoids / HeLa cells / Hybridization / Immunoprecipitation / Immunosuppressive agents / Inflammation / Kinases / lncRNA / NF-κB / NF-κB protein / Non-coding RNA / Patients / Pediatrics / Pharmacology / Proteins / Signal transduction / Transcription factors / Tumor necrosis factor-TNF / Tumor necrosis factor-α / Western blotting