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Details on Person ATP-binding cassette transporter A1 (ABCA1) is a target of m...
| Class:Id | Summation:9624914 |
|---|---|
| _displayName | ATP-binding cassette transporter A1 (ABCA1) is a target of m... |
| _timestamp | 2019-08-14 03:03:17 |
| created | [InstanceEdit:9624918] Shamovsky, Veronica, 2018-10-16 |
| literatureReference | [LiteratureReference:9629136] Asymptomatic individuals with high HDL-C levels overexpress ABCA1 and ABCG1 and present miR-33a dysregulation in peripheral blood mononuclear cells [LiteratureReference:9629108] MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis [LiteratureReference:9629109] miR-33 links SREBP-2 induction to repression of sterol transporters [LiteratureReference:9629123] MicroRNA-33 encoded by an intron of sterol regulatory element-binding protein 2 (Srebp2) regulates HDL in vivo [LiteratureReference:9609456] Sterol-dependent transactivation of the ABC1 promoter by the liver X receptor/retinoid X receptor [LiteratureReference:9611781] Differential regulation of gene expression by LXRs in response to macrophage cholesterol loading [LiteratureReference:9624929] MiR-33 contributes to the regulation of cholesterol homeostasis |
| modified | [InstanceEdit:9629140] Shamovsky, Veronica, 2018-11-19 [InstanceEdit:9634037] Shamovsky, Veronica, 2019-01-03 [InstanceEdit:9657834] Shamovsky, Veronica, 2019-08-09 [InstanceEdit:9658262] Shamovsky, Veronica, 2019-08-12 [InstanceEdit:9658425] Shamovsky, Veronica, 2019-08-14 |
| text | ATP-binding cassette transporter A1 (ABCA1) is a target of micro RNA 33 (miR-33) (Rayner KJ et al. 2010; Marquart TJ et al. 2010; Najafi-Shoushtari SH et al.2010; Horie T et al. 2010; Zaiou M et al. 2018). The miR33 family consists of two intronic miRNAs, miR-33a and miR-33b, which are encoded within the introns of the sterol regulatory element-binding proteins (SREBP) 2 and 1 genes, respectively (Marquart TJ et al. 2010; Najafi-Shoushtari SH et al.2010; Horie T et al. 2010). Under conditions that stimulate SREBP transcription, miR-33a/b are co-expressed with their host genes and reciprocally regulate genes such as ABCA1 that are involved in cellular cholesterol efflux and high-density lipoprotein (HDL) biogenesis (Marquart TJ et al. 2010; Najafi-Shoushtari SH et al.2010; Horie T et al. 2010). Expression of the ABCA1 gene is induced by oxysterol-activated transcription factors liver X receptor α (LXRα, NR1H3) and LXRβ (NR1H2) and their heterodimeric partners, retinoid X receptors (RXR) via functional LXR response element (LXRE) in target genes (Costet P et al. 2000; Ignatova ID et al. 2013). miR-33 was found to suppress expression of ABCA1 in human macrophages (THP-1) and hepatocytes (HepG2, Hep3B ) treated with a synthetic agonist, T0901317, of LXRs (Rayner KJ et al. 2010; Marquart TJ et al. 2010). Inhibition of endogenous miR-33 by anti-miR-33 increased the expression of ABCA1 in THP-1 and HepG2 cells (Rayner KJ et al. 2010). In vivo studies showed that liver ABCA1 protein and serum HDL-C levels were higher in miR-33-deficient mice than in control mice (Horie T et al. 2010). In line with this, a study reported that healthy individuals with high HDL-C levels often overexpress ABCA1 and ABCG1 and show a decrease of miR-33a in their peripheral blood mononuclear cells (Scherrer DZ et al. 2015). Analysis of the 3' untranslated region (3'UTR) of ABCA1 identified sequences that are partially complementary to miR-33 sequences (Marquart TJ et al. 2010). Importantly, these sequences are evolutionarily conserved across animal species (Marquart TJ et al. 2010). Further, a 3'UTR luciferase reporter assay showed that miR-33 directly binds the ABCA1 3′UTR when human embryonic kidney (HEK293T) cells were cotransfected with luciferase reporter constructs fused to the 3′UTR of ABCA1 and control miR or miR-33 (Rayner KJ et al. 2010; Horie T et al. 2010; Najafi-Shoushtari SH et al. 2010). Mutation in the potential binding site in the 3′-UTR abolished the effect of miR-33 (Horie T et al. 2010). The Reactome event describes the miR-33- regulated translation of ABCA1 mRNA in response to NR1H2,3 natural ligands. The annotation is based on studies with T0901317, the synthetic agonist of NR1H2,3 (Rayner KJ et al. 2010; Marquart TJ et al. 2010). |
| (summation) | [Reaction:9624925] miR-33 binds to the 3'UTR of the ABCA1 mRNA [Homo sapiens] |
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