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).
Rihn, BH, Bakillah, A, Zaiou, M
Baldán, A, Ory, DS, Marquart, TJ, Allen, RM
Najafi-Shoushtari, SH, Cohen, DE, Kristo, F, Li, Y, Shioda, T, Näär, AM, Gerszten, RE
Suárez, Y, Dávalos, A, Fitzgerald, ML, Moore, KJ, Parathath, S, Fisher, EA, Fernández-Hernando, C, Tamehiro, N, Rayner, KJ
Yokode, M, Ono, K, Kita, T, Kimura, T, Kinoshita, M, Hasegawa, K, Nishi, H, Iwanaga, Y, Nagao, K, Marusawa, H, Nakamura, T, Horie, T, Kuwabara, Y, Horiguchi, M
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