Effect of depletion of MALAT1 on gene expression during LPS stimulation on THP-1 derived differentiated macrophages

Long non-coding RNAs (lncRNAs) are known for their diverse roles in regulating gene expression, cellular functions, and metabolic pathways. Among them, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been extensively studied in cancer and inflammation. Here, we report a newly discovered interaction between MALAT1 and HADHB—a key enzyme in mitochondrial fatty acid oxidation (FAO)—which reveals additional regulatory roles for MALAT1 in human macrophages. Our findings show that MALAT1 binds to hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta (HADHB), significantly enhancing its thiolase activity and its expression during the inflammation.By targeting HADHB, MALAT1 influences both inflammatory and metabolic pathways, providing insights into its potential as a therapeutic target for modulating macrophage activity and metabolic balance in chronic inflammatory diseases. This study not only identifies HADHB as a new target of MALAT1 but also underscores the conserved functional roles of lncRNAs across species, particularly in immune and metabolic regulation.