# LncRNA HOTAIR promotes LPS-induced inflammatory responses by activating the NF-κB pathway

## TL;DR

This study shows that the long non-coding RNA HOTAIR worsens lung inflammation by activating the NF-κB pathway, suggesting it could be a target for treating acute lung injury.

## Contribution

The study identifies HOTAIR as a novel regulator of NF-κB-driven inflammation in acute lung injury.

## Key findings

- HOTAIR overexpression increases NF-κB signaling and pro-inflammatory cytokine production in A549 cells.
- Knockdown of HOTAIR reduces LPS-induced lung injury and inflammation in mice.
- HOTAIR promotes phosphorylation of IκBα and p65, enhancing NF-κB activation.

## Abstract

Acute lung injury (ALI) is a disease with an excessive inflammatory response triggered by activating the NF-κB signaling pathway. Our study aims to investigate the role of the long non-coding RNA HOTAIR in ALI-associated hyperinflammation, providing evidence for HOTAIR as a potential therapeutic target for ALI. Here, we examined the contribution of HOTAIR to LPS-induced lung injury using both A549 cell and murine models. LPS stimulation markedly increased HOTAIR expression in A549 cells, accompanied by reduced cell viability and elevated secretion of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Overexpression of HOTAIR further amplified NF-κB signaling, as indicated by increased phosphorylation of IκBα and p65 and enhanced nuclear translocation of p65, whereas silencing HOTAIR effectively reversed these effects. In vivo, knockdown of HOTAIR significantly mitigated LPS-induced lung injury, reduced inflammatory cytokine production, and suppressed NF-κB activation in mice. Our findings reveal the contribution of HOTAIR to NF-κB–driven inflammatory injury in ALI, offering insight into its regulatory role and informing future exploration of targeted therapeutic approaches.