LncRNA kcnq1ot1 promotes lipid accumulation and accelerates atherosclerosis via functioning as a ceRNA through the miR-452-3p/HDAC3/ABCA1 axis
| Autor: | Min Tao, Xiao-Hua Yu, Qi-Xian Liu, Xiao-Dan Xu, Lei Chen, Xian-Xia Liu, Meng-Wen Shi, Jiao-Jiao Chen, Wen-Yi Deng, Kun Ren |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
Cancer Research THP-1 Cells Immunology Down-Regulation Histone Deacetylases Article Cellular and Molecular Neuroscience chemistry.chemical_compound Apolipoproteins E Downregulation and upregulation Animals Humans THP1 cell line lcsh:QH573-671 Dyslipidaemias Gene knockdown Base Sequence KCNQ1OT1 biology lcsh:Cytology Cholesterol Cholesterol HDL Biological Transport Cell Biology Atherosclerosis Lipid Metabolism HDAC3 Plaque Atherosclerotic Cell biology Mice Inbred C57BL MicroRNAs chemistry ABCA1 Macrophages Peritoneal Long non-coding RNAs biology.protein RNA Long Noncoding lipids (amino acids peptides and proteins) Signal transduction ATP Binding Cassette Transporter 1 Signal Transduction |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 11, Iss 12, Pp 1-14 (2020) |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-020-03263-6 |
| Popis: | Kcnq1 overlapping transcript 1 (kcnq1ot1), an imprinted antisense lncRNA in the kcnq1 locus, acts as a potential contributor to cardiovascular disease, but its role in atherosclerosis remains unknown. The aim of this study was to explore the effects of kcnq1ot1 on atherogenesis and the underlying mechanism. Our results showed that kcnq1ot1 expression was significantly increased in mouse aorta with atherosclerosis and lipid-loaded macrophages. Lentivirus-mediated kcnq1ot1 overexpression markedly increased atherosclerotic plaque area and decreased plasma HDL-C levels and RCT efficiency in apoE−/− mice fed a Western diet. Upregulation of kcnq1ot1 also reduced the expression of miR-452-3p and ABCA1 but increased HDAC3 levels in mouse aorta and THP-1 macrophages. Accordingly, kcnq1ot1 overexpression inhibited cholesterol efflux and promoted lipid accumulation in THP-1 macrophages. In contrast, kcnq1ot1 knockdown protected against atherosclerosis in apoE−/− mice and suppressed lipid accumulation in THP-1 macrophages. Mechanistically, kcnq1ot1 enhanced HDAC3 expression by competitively binding to miR-452-3p, thereby inhibiting ABCA1 expression and subsequent cholesterol efflux. Taken together, these findings suggest that kcnq1ot1 promotes macrophage lipid accumulation and accelerates the development of atherosclerosis through the miR-452-3p/HDAC3/ABCA1 pathway. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink