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Research Paper|Volume 16, Issue 18|pp 12510—12524

LncRNA DANCR promotes macrophage lipid accumulation through modulation of membrane cholesterol transporters

Guo-Jun Zhao1, Yu Wang1, Jun-Hong An2, Wan-Ying Tang3, Xiao-Dan Xu4, Kun Ren5,6
  • 1Affiliated Qingyuan Hospital, Guangzhou Medical University (Qingyuan People’s Hospital), Qingyuan 511518, Guangdong, China
  • 2College of Medicine, Dali University, Dali 671003, Yunnan, China
  • 3Department of Physiology, Institute of Neuroscience Research, Hengyang Key Laboratory of Neurodegeneration and Cognitive Impairment, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China
  • 4Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui, P.R. China
  • 5College of Nursing, Anhui University of Chinese Medicine, Hefei 230012, Anhui, P.R. China
  • 6Institute of Clinical Medicine, The Second Affiliated Hospital of Hainan Medical University, Haikou 570100, Hainan, P.R. China
* Equal contribution
Received: May 18, 2023Accepted: May 30, 2024Published: July 2, 2024
https://doi.org/10.18632/aging.205992

Copyright: © 2024 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.