LncRNA kcnq1ot1 promotes lipid accumulation and accelerates atherosclerosis via functioning as a ceRNA through the miR-452-3p/HDAC3/ABCA1 axis

Yu, Xiaohua; Deng, Wenyi; Chen, Jiaojiao; Xu, Xiaodan; Liu, Xian-Xia; Chen, Lei; Shi, Meng-Wen; Liu, Qi-Xian; Tao, Min; Ren, Kewei

doi:10.1038/s41419-020-03263-6

Cited by 70 publications

(51 citation statements)

References 48 publications

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“…Our results showed that CTRP12 polarized macrophages towards an M2 phenotype and attenuated vascular inflammation through the miR-155-5p/LXRα pathway, thereby providing another important mechanism for its antiatherogenic action. A growing body of evidence has indicated that lncRNAs are pivotal regulators of atherogenesis 62 , 63 . More recently, Wang et al reported that the expression levels of CTBP1-AS2, a lncRNA, were significantly decreased in the serum of patients with atherosclerosis, and its overexpression inhibits proliferation and promotes autophagy in human aortic smooth muscle cells challenged with ox-LDL 64 .…”

Section: Discussionmentioning

confidence: 99%

CTRP12 ameliorates atherosclerosis by promoting cholesterol efflux and inhibiting inflammatory response via the miR-155-5p/LXRα pathway

et al. 2021

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C1q tumor necrosis factor-related protein 12 (CTRP12), a conserved paralog of adiponectin, is closely associated with cardiovascular disease. However, little is known about its role in atherogenesis. The aim of this study was to examine the influence of CTRP12 on atherosclerosis and explore the underlying mechanisms. Our results showed that lentivirus-mediated CTRP12 overexpression inhibited lipid accumulation and inflammatory response in lipid-laden macrophages. Mechanistically, CTRP12 decreased miR-155-5p levels and then increased its target gene liver X receptor α (LXRα) expression, which increased ATP binding cassette transporter A1 (ABCA1)- and ABCG1-dependent cholesterol efflux and promoted macrophage polarization to the M2 phenotype. Injection of lentiviral vector expressing CTRP12 decreased atherosclerotic lesion area, elevated plasma high-density lipoprotein cholesterol levels, promoted reverse cholesterol transport (RCT), and alleviated inflammatory response in apolipoprotein E-deficient (apoE−/−) mice fed a Western diet. Similar to the findings of in vitro experiments, CTRP12 overexpression diminished miR-155-5p levels but increased LXRα, ABCA1, and ABCG1 expression in the aortas of apoE−/− mice. Taken together, these results suggest that CTRP12 protects against atherosclerosis by enhancing RCT efficiency and mitigating vascular inflammation via the miR-155-5p/LXRα pathway. Stimulating CTRP12 production could be a novel approach for reducing atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

CTRP12 ameliorates atherosclerosis by promoting cholesterol efflux and inhibiting inflammatory response via the miR-155-5p/LXRα pathway

et al. 2021

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“…Since many studies have confirmed lncRNAs’ regulatory roles in lipid homeostasis, some researchers think they may take part in the development of atherosclerosis. LncRNA KCNQ1OT1 could inhibit cholesterol efflux and promote lipid accumulation in macrophages via the miR-452-3p/HDAC3/ABCA1 pathway, and, thus, contribute to the development of atherosclerosis ( Yu et al, 2020 ). A key node in atherosclerosis is when macrophages uptake lipoproteins and form foam cells ( Tabas and Bornfeldt, 2020 ).…”

Section: The Potential Of Lncrnas As Therapeutic Targets Of Related Diseases Induced By Adipocyte Dysfunctionmentioning

confidence: 99%

Long Noncoding RNAs: Novel Important Players in Adipocyte Lipid Metabolism and Derivative Diseases

Zhang

Liu

et al. 2021

Front. Physiol.

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Obesity, a global public health issue, is characterized by excessive adiposity and is strongly related to some chronic diseases including cardiovascular diseases and diabetes. Extra energy intake-induced adipogenesis involves various transcription factors and long noncoding RNAs (lncRNAs) that control lipogenic mRNA expression. Currently, lncRNAs draw much attention for their contribution to adipogenesis and adipose tissue function. Increasing evidence also manifests the pivotal role of lncRNAs in modulating white, brown, and beige adipose tissue development and affecting the progression of the diseases induced by adipose dysfunction. The aim of this review is to summarize the roles of lncRNAs in adipose tissue development and obesity-caused diseases to provide novel drug targets for the treatment of obesity and metabolic diseases.

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“…It has been found that lncRNA APF targets the regulation of miR-188-3p, thereby affecting the expression of ATG7 in autophagy, which can effectively reduce the area of myocardial infarction, prevent HF, and prolong survival time (13). LncRNA kcnq1ot1 was demonstrated to increase HDAC3 expression by competitively binding to miR-452-3p, followed by the inhibition of ABCA1 and cholesterol efflflux, promoted macrophage lipid accumulation and accelerated the development of atherosclerosis (14). The above findings highlighted the importance of ceRNA network, a global view of lncRNAmediated ceRNA network may help researchers comprehensively understand the pathophysiological process of cardiovascular diseases.…”

Section: Introductionmentioning

confidence: 99%

Novel lncRNA-miRNA-mRNA Competing Endogenous RNA Triple Networks Associated Programmed Cell Death in Heart Failure

Zheng

Zhang

et al. 2021

Front. Cardiovasc. Med.

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Objective: Increasing evidence has uncovered the roles of lncRNA-miRNA-mRNA regulatory networks in cardiovascular diseases. However, the crosstalk between ceRNA networks and development of heart failure (HF) remains unclear. This study was to investigate the role of lncRNA-mediated ceRNA networks in the pathophysiological process of HF and its potential regulatory functions on programmed cell death.Methods: We firstly screened the GSE77399, GSE52601 and GSE57338 datasets in the NCBI GEO database for screening differentially expressed lncRNAs, miRNAs and mRNAs. lncRNA-miRNA-mRNA regulatory networks based on the ceRNA theory were subsequently constructed. GO and KEGG enrichment analysis was conducted to predict potential biological functions of mRNAs in ceRNA networks. Differentially expressed mRNAs were then interacted with programmed cell death related genes. lncRNA-mediated ceRNA regulatory pathways on programmed cell death were validated with qRT-PCR testing.Results: Based on our bioinformatic analysis, two lncRNAs, eight miRNAs and 65 mRNAs were extracted to construct two lncRNAs-mediated ceRNA networks in HF. Biological processes and pathways were enriched in extracellular matrix. Seven lncRNA-mediated ceRNA regulatory pathways on programmed cell death, GAS5/miR-345-5p/ADAMTS4, GAS5/miR-18b-5p/AQP3, GAS5/miR-18b-5p/SHISA3, GAS5/miR-18b-5p/C1orf105, GAS5/miR-18b-5p/PLIN2, GAS5/miR-185-5p/LPCAT3, and GAS5/miR-29b-3p/STAT3, were finally validated.Conclusions: Two novel ceRNA regulatory networks in HF were discovered based on our bioinformatic analysis. Based on the interaction and validation analysis, seven lncRNA GAS5-mediated ceRNA regulatory pathways were hypothesized to impact programmed cell death including seven for apoptosis, three for ferroptosis, and one for pyroptosis. Upon which, we provided novel insights and potential research plots for bridging ceRNA regulatory networks and programmed cell death in HF.

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LncRNA kcnq1ot1 promotes lipid accumulation and accelerates atherosclerosis via functioning as a ceRNA through the miR-452-3p/HDAC3/ABCA1 axis

Cited by 70 publications

References 48 publications

CTRP12 ameliorates atherosclerosis by promoting cholesterol efflux and inhibiting inflammatory response via the miR-155-5p/LXRα pathway

CTRP12 ameliorates atherosclerosis by promoting cholesterol efflux and inhibiting inflammatory response via the miR-155-5p/LXRα pathway

Long Noncoding RNAs: Novel Important Players in Adipocyte Lipid Metabolism and Derivative Diseases

Novel lncRNA-miRNA-mRNA Competing Endogenous RNA Triple Networks Associated Programmed Cell Death in Heart Failure

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