Basic Information
Regular Relationship :
Phenotype/DiseaseSpecieAtherosclerosis
CeRNA1PCA3[LncRNA]
miRNAmiR-140-5p[miRNA]
CeRNA2RFX7[mRNA]
Tissue/Cell lineatherosclerosis cells
SpecieHomo sapiens (human)
CitationBiochim Biophys Acta Mol Cell Biol Lipids. 2021 May;1866(5):158904. doi: 10.1016/j.bbalip.2021.158904. Epub 2021 Feb 10.
Reference title
Long non-coding RNA PCA3 inhibits lipid accumulation and atherosclerosis through the miR-140-5p/RFX7/ABCA1 axis.
Experimental verification
qPCR;Western blot;Chromatin immunoprecipitation;
Functional description
OBJECTIVE: The purpose of this study was to explore the role of long noncoding RNA (lncRNA) prostate cancer antigen 3 (PCA3) in atherosclerosis and the underlying mechanism. METHODS: The Gene Expression Omnibus (GEO) datasets were used to divide differentially expressed lncRNAs, microRNAs (miRNAs), and mRNAs. The expression of PCA3, miR-140-5p, RFX7 and ABCA1 were determined by qPCR or Western blot in ox-LDL-treated macrophages. Macrophage lipid accumulation s was evaluated using the Oil Red O staining and high-performance liquid chromatography. Target relationships among PCA3, miR-140-5p, RFX7, and ABCA1 promoter area were validated via dual-luciferase reporter gene assay or chromatin immunoprecipitation assay. The apoE(-/-) mouse model in vivo was designed to evaluate the effect of PCA3 on the reverse cholesterol transport (RCT) and atherosclerosis. RESULTS: PCA3 was down-regulated in foam cells, whereas miR-140-5p was highly expressed. Overexpression of PCA3 promoted ABCA1-mediated cholesterol efflux and reduced lipid accumulation in macrophages. Besides, RFX7 bound to the ABCA1 promoter and increased ABCA1 expression. Targeted relationships and interactions on the expression between miR-140-5p and PCA3 or RFX7 were elucidated. PCA3 up-regulated ABCA1 expression by binding to miR-140-5p to up-regulate RFX7 and ABCA1 expression in macrophages. PCA3 promoted RCT and impeded the progression of atherosclerosis by sponging miR-140-5p in apoE(-/-) mice. Meanwhile, miR-140-5p also inhibit ABCA1 expression via downregulation of RFX7 to impede RCT and aggravate atherosclerosis. CONCLUSIONS: lncRNA PCA3 promotes ABCA1-mediated cholesterol efflux to inhibit atherosclerosis through sponging miR-140-5p and up-regulating RFX7.
Annotations
External Annotation for PCA3 |
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LncRNA-associated competing triplets and functions. |
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Comprehensive experimentally supported associations between lncRNA and human cancer. |
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Infer genomic variations that disturb lncRNA-associated ceRNA regulation.. |
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Provide and annotate disease or phenotype-associated variants in human long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) or their regulatory elements. |
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Providing cellular-specific lncRNA-associated ceRNA networks predicted via high-throughput analysis of single-cell genomic data. |
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Information on all annotated and predicted human genes. |
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Gene nomenclature, gene families and associated resources (genomic, proteomic, phenotypic information). |
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Genome browser for vertebrate genomes. |
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An annotated collection of all publicly available DNA sequences. |
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A wiki-based platform for community curation of human long non-coding RNAs. |
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An integrated knowledge database dedicated to non-coding RNAs. |
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An integrated database of human annotated lncRNA transcripts. |
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Comprehensive annotations of eukaryotic long non-coding RNAs. |
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Comprehensive experimentally supported associations between lncRNA and human cancer. |
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A comprehensive, authoritative compendium of human genes and genetic phenotypes. |
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The catalogue of somatic mutations in cancer. |
