%A Zhao, Guo-Jun 
%A Wang, Yu 
%A An, Jun-Hong 
%A Tang, Wan-Ying 
%A Xu, Xiao-Dan 
%A Ren, Kun 
%D 2024
%T LncRNA DANCR promotes macrophage lipid accumulation through modulation of membrane cholesterol transporters
%! LncRNA DANCR promotes macrophage lipid accumulation through modulation of membrane cholesterol transporters
%K DANCR, miR-33a, lipid accumulation, cholesterol transport, macrophage
%X The progression of atherosclerosis (AS), the pathological foundation of coronary artery disease (CAD), is featured by massive lipid deposition in the vessel wall. LncRNAs are implicated in lipid disorder and AS, whereas the specific role of lncRNA DANCR in atherogenesis remains unknown. Here, we demonstrated that DANCR promotes macrophage lipid accumulation by regulating the expression of membrane cholesterol transport proteins. qPCR showed that compared to control groups, CAD patients and atherosclerotic mice had higher DANCR levels. Treating human THP-1 macrophages and mouse RAW264.7 macrophages with ox-LDL significantly upregulated the expression levels of DANCR. Oil Red O staining showed that the silence of DANCR robustly reduced, while overexpression of DANCR significantly increased the numbers and size of lipid droplets in ox-LDL-treated THP-1 macrophages. In contrast, the opposite phenomena were observed in DANCR overexpressing cells. The expression of ABCA1, ABCG1, SR-BI, and NBD-cholesterol efflux was increased obviously by DANCR inhibition and decreased by DANCR overexpression, respectively. Furthermore, transfection with DANCR siRNA induced a robust decrease in the levels of CD36, SR-A, and Dil-ox-LDL uptake, while DANCR overexpression amplified the expression of CD36, SR-A and the uptake of Dil-ox-LDL in lipid-laden macrophages. Lastly, we found that the effects of DANCR on macrophage lipid accumulation and the expression of membrane cholesterol transport proteins were not likely related to miR-33a. The present study unraveled the adverse role of DANCR in foam cell formation and its relationship with cholesterol transport proteins. However, the competing endogenous RNA network underlying these phenomena warrants further exploration.
%U https://doi.org/10.18632/aging.205992
%J Aging
%0 Journal Article
%V 16
%N 18
%P 12510-12524
%R 10.18632/aging.205992
%@ 1945-4589