# A systems approach to target discovery identifies the role of lncRNA-SPANXA2-OT1 in macrophage chemotaxis

## TL;DR

A human-specific RNA called SPANXA2-OT1 regulates inflammation in macrophages linked to heart disease, suggesting potential as a treatment target.

## Contribution

Identifies SPANXA2-OT1 as a novel human-specific lncRNA regulator of macrophage chemotaxis and inflammation in coronary artery disease.

## Key findings

- SPANXA2-OT1 is induced by inflammation and regulates chemokine expression in macrophages.
- SPANXA2-OT1 functions as a microRNA-338 sponge to modulate IL-8 expression.
- The lncRNA is a human-specific regulator of inflammatory pathways in coronary artery disease.

## Abstract

Coronary artery disease (CAD) is the leading cause of mortality worldwide, with macrophages playing a central role in shaping the inflammatory environment through cytokines, chemokines, and other mediators. Long noncoding RNAs (lncRNAs) are emerging as key regulators of cellular processes owing to their interactions with DNA, RNA, microRNAs, and proteins, which positions them to be promising therapeutic targets. Through integrative transcriptomic analysis, we identified SPANXA2-OT1 as a primate-specific lncRNA with a potential role in macrophage-mediated inflammation in CAD. Functional studies in primary human macrophages demonstrated that SPANXA2-OT1 was induced by inflammatory stimulation, localized to the cytoplasm, and exerted regulatory effects on chemokine expression and macrophage chemotaxis. Mechanistically, SPANXA2-OT1 acted as a molecular sponge for microRNA-338, thereby influencing the expression of IL-8, a critical mediator of monocyte recruitment and inflammatory signaling. Collectively, these findings establish SPANXA2-OT1 as a human-specific regulator of inflammatory pathways in CAD and highlight its translational potential as both a biomarker and therapeutic target.

Human-specific RNA SPANXA2-OT1 regulates macrophage-driven inflammation in coronary artery disease, offering promise as a biomarker and therapeutic target to reduce cardiovascular risk.