LncRNA MALATI regulates oxLDL-induced CD36 expression via activating β-catenin

The expression of scavenger receptors in macrophages regulating lipid uptake plays an important role in foam cell formation and the subsequent atherosclerotic plaque formation. Long non-coding RNA MALATI is abundantly expressed in THP-1-derived macrophages, and oxidized low-density lipoprotein promotes its transcription by qRT-PCR and RNA FISH detection. Through chemical inhibitor treatments and by performing a dual luciferase reporter analysis, we found that oxLDL induces MALATI transcription through the NF-KB pathway. The knockdown of MALAT1 using siRNA transfection affects lipid uptake in macrophages. To understand the details, we checked the scavenger receptors, which mainly control lipid uptake, and found that MALATI knockdown decreased CD36 expression. Additionally, we also incubated macrophages with actinomycin D, combined with a dual luciferase reporter analysis, and we found that MALATI influenced CD36 expression at the transcription level. We aim to investigate the detailed mechanism by which MALATI promotes CD36 transcription, and thus, we designed and synthesized biotin-TEG labeled oligonucleotides to precipitate the MALATI RNA-DNA -protein complex in vivo. Combined with SDS-PAGE electrophoresis and a subsequent mass spectra analysis, B-catenin, a transcription factor that promotes CD36 transcription, was found in the complex. By performing R-IPs, we validated that B-catenin was bound to MALATI under the oxLDL treatment. In addition, using VAX939, a chemical inhibitor of B-catenin, MALATI was demonstrated to promote CD36 transcription partly via 13catenin. We also performed chips to detect whether MALATI affects B-catenin accumulation in the binding sites of the CD36 promoter and found that MALAT1 knockdown decreases B-catenin binding to the CD36 promoter and vice versa. In conclusion, oxLDL induced MALATI transcription and MALATI recruits fl-catenin to binding sites on the CD36 promoter to induce CD36 expression, which enhances lipid uptake in macrophages. (C) 2017 Elsevier Inc. All rights reserved.