The long noncoding RNA lnc-FAM164A1-ACLY axis promotes pro-inflammatory responses in human primary macrophages: a...

Macrophages play a key role in inflammatory diseases. We aimed to identify long noncoding RNAs that regulate pro-inflammatory activation of human macrophages.

We performed human lncRNA microarray analysis in LPS-stimulated primary human macrophages. We then carried out loss-of-function and gain-of-function experiments, luciferase reporter assays, RNA pulldown, RNA immunoprecipitation, and mouse endotoxemia studies, including humanized mouse models.

We identified 11 lncRNAs that were significantly increased by LPS. Among them, lnc-FAM164A1 was selected for further study. Silencing of lnc-FAM164A1 by antisense oligonucleotides or siRNA reduced the LPS-induced expression of pro-inflammatory cytokines, including CCL2, IL-6, and TNF-α. In contrast, enforced expression of lnc FAM164A1 enhanced inflammatory responses in human and mouse macrophages. lnc FAM164A1 also promoted NF-κB-related signaling. RNA pulldown and RNA immunoprecipitation identified ACLY as an lnc-FAM164A1-associated protein. ACLY silencing reduced the inflammatory effects induced by lnc-FAM164A1.

These findings support that human lnc-FAM164A1 promotes pro-inflammatory activation of macrophages through its interaction with ACLY and NF-κB-related signaling.