The DOI matches its Crossref record; 30 of the 31 references it cites were found in a registry or an index.
MicroRNA-33 and the SREBP Host Genes Cooperate to Control Cholesterol Homeostasis
Open accessAbstract
miR-33 in Cholesterol Control: With the well-established link between serum cholesterol levels and cardiovascular disease and the availability of effective cholesterol-lowering drugs, cholesterol screening has rapidly become a routine part of health care. Yet, much remains to be learned about how cholesterol levels are regulated at the cellular level (see the Perspective by Brown et al. ). Now, Najafi-Shoushtari et al. (p. 1566 , published online 13 May) and Rayner et al. (p. 1570 , published online 13 May) have discovered a new molecular player in cholesterol control—a small noncoding RNA that, intriguingly, is embedded within the genes coding for sterol regulatory element-binding proteins (SREBPs), transcription factors already known to regulate cholesterol levels. This microRNA, called miR-33, represses expression of the adenosine triphosphate–binding cassette transporter A1, a protein that regulates synthesis of high-density lipoprotein (HDL, or “good” cholesterol) and that helps to remove “bad” cholesterol from the blood. Reducing the levels of miR-33 in mice boosted serum HDL levels, suggesting that manipulation of this regulatory circuit might be therapeutically useful.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Pharmacological inhibition of miR-33 increased plasma high-density lipoprotein cholesterol levels in mice (Horie et al., 2010;Najafi-Shoushtari et al., 2010;Rayner et al., 2011a) and primates (Rayner et al., 2011b;Rottiers et al., 2013), leading to a marked reduction of atherosclerosis phenotypes.”
From microRNA-33 Regulates ApoE Lipidation and Amyloid-β Metabolism in the Brain (2015) · cites this paper as Najafi-Shoushtari et al., 2010
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“in vivo antagonism or genetic deletion of miR-33 enhances hepatic ABCA1 expression and increases circulating HDL-cholesterol (HDL-C) (Marquart et al., 2010; Najafi-Shoushtari et al., 2010; Rayner et al., 2010).”
From Genetic dissection of the impact of miR-33a and miR-33b during the progression of atherosclerosis (2017) · cites this paper as Najafi-Shoushtari et al., 2010
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“These differences in miRNA expression vary between cell types suggesting that the role of miR-33b in the liver, where miR-33 is most highly expressed both in our mouse model and in human tissues (Najafi-Shoushtari et al., 2010), and other tissues may be considerably more important.”
From Genetic dissection of the impact of miR-33a and miR-33b during the progression of atherosclerosis (2017) · cites this paper as Najafi-Shoushtari et al., 2010
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In miR-33a knockout mice or when miR-33a is suppressed by synthetic nucleic acids such as antagomirs, the expression of ABCA1 in macrophages and the liver is increased 11 - 15) .”
From Critical Role of microRNA-33a/b in Cardiovascular and Metabolic Disease: Molecular Mechanisms and Therapeutic Perspectives (2026) · cites this paper as [11]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“MicroRNA (miR)-33 is known to target ABCA1 and ABCG1 in vivo.”
From MicroRNA‐33 Deficiency Reduces the Progression of Atherosclerotic Plaque in ApoE −/− Mice (2012) · cites this paper as [17]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Two miR-33 genes are present in humans: miR-33b, which is present in intron 17 of the Srebp-1 gene on chromosome 17, and miR-33a, which is located in intron 16 of the Srebp-2 gene on chromosome 22.”
From miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling (2011) · cites this paper as [13]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“We and others have recently established that, during sterol-limited states, miR-33a is coincidentally generated with Srebp-2 transcription and works to increase cellular cholesterol levels by limiting cholesterol export through the down-regulation of ABC transporters, ABCA1 and ABCG1 (12–14).”
From miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling (2011) · cites this paper as [13]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“miR-33a and miR-33b are intronic miRNAs encoded within the SREBP-2 and SREBP-1 genes respectively (Marquart et al., 2010; Najafi-Shoushtari et al., 2010; Rayner et al., 2010).”
From Genetic dissection of the impact of miR-33a and miR-33b during the progression of atherosclerosis (2017) · cites this paper as Najafi-Shoushtari et al., 2010
The cited source says what the claim attributes to it.
In the citing paper
“This work led to the demonstration that miR-33a and miR-33b are co-transcribed along with SREBP-2 and SREBP-1, and work in concert with their host genes to help maintain proper lipid levels within the cell (Davalos et al., 2011; Marquart et al., 2010; Najafi-Shoushtari et al., 2010; Rayner et al., 2010).”
From Genetic dissection of the impact of miR-33a and miR-33b during the progression of atherosclerosis (2017) · cites this paper as Najafi-Shoushtari et al., 2010
The cited source says what the claim attributes to it.
In the citing paper
“The most well-known target gene of miR-33a/b is ATP-binding cassette subfamily A member 1 (ABCA1).”
From Critical Role of microRNA-33a/b in Cardiovascular and Metabolic Disease: Molecular Mechanisms and Therapeutic Perspectives (2026) · cites this paper as [11]
The cited source says what the claim attributes to it.
In the citing paper
“Recent reports, including ours, have indicated that miR-33 controls cholesterol homeostasis based on knockdown experiments using antisense technology.16–18”
From MicroRNA‐33 Deficiency Reduces the Progression of Atherosclerotic Plaque in ApoE −/− Mice (2012) · cites this paper as [17]
The cited source says what the claim attributes to it.
In the citing paper
“We and others provided identification of a highly conserved miRNA family, miR-33, within the intronic sequences of the Srebp genes in organisms ranging from Drosophila to humans (11–14).”
From miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling (2011) · cites this paper as [13]
The cited source says what the claim attributes to it.
In the citing paper
“In mice, however, there is only one miR-33 gene, which is conserved with human miR-33a and located within intron 15 of the mouse Srebp-2 gene.”
From miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling (2011) · cites this paper as [13]
The cited source says what the claim attributes to it.
In the citing paper
“Importantly, these pathways regulate circulating HDL levels through their roles in HDL biogenesis and cellular cholesterol efflux (12–14).”
From miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling (2011) · cites this paper as [13]
In the citing paper
“These microRNAs participate in the regulation of cholesterol synthesis, fatty acid metabolism, and insulin signaling.”
From The Vasculature in Prediabetes (2018) · cites this paper as [143]
In the citing paper
“They are co-transcribed and act in conjunction with their host genes, Srebp1 and Srebp2, to regulate cholesterol synthesis.”
From The Vasculature in Prediabetes (2018) · cites this paper as [143]
In the citing paper
“Furthermore, an intronic microRNA located within Srebf2 gene, miR-33, inhibits the expression of Abca1 (Najafi-Shoushtari et al., 2010; Rayner et al., 2010).”
From Inhibition of cholesterol biosynthesis through RNF145-dependent ubiquitination of SCAP (2017) · cites this paper as Najafi-Shoushtari et al., 2010
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Bartel (2004) · doi:10.1016/s0092-8674(04)00045-5 · Cited by 34,714
MicroRNAs: Target Recognition and Regulatory Functions
Bartel, D. P. (2009) · Cell · doi:10.1016/j.cell.2009.01.002 · Cited by 20,068
MicroRNAs: small RNAs with a big role in gene regulation
He, L., & Hannon, G. J. (2004) · Nature Reviews Genetics · doi:10.1038/nrg1379 · Cited by 7,118
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15593 · Cited by 4,794
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215593 · Cited by 4,092
Silencing of microRNAs in vivo with ‘antagomirs’
Krützfeldt, J., Rajewsky, N., Braich, R., Rajeev, K. G., Tuschl, T., Manoharan, M., & Stoffel, M. (2005) · Nature · doi:10.1038/nature04303 · Cited by 3,949
Brown, M. S., & Goldstein, J. L. (1997) · Cell · doi:10.1016/s0092-8674(00)80213-5 · Cited by 3,834
Identification of Mammalian microRNA Host Genes and Transcription Units
Rodriguez, A., Griffiths-Jones, S., Ashurst, J. L., & Bradley, A. (2004) · Genome Research · doi:10.1101/gr.2722704 · Cited by 2,128
miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting
Esau, C., Davis, S., Murray, S. F., Yu, X. X., Pandey, S. K., Pear, M., Watts, L., Booten, S. L., Graham, M., McKay, R., et al. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.005 · Cited by 2,082
LNA-mediated microRNA silencing in non-human primates
Elmén, J., Lindow, M., Schütz, S., Lawrence, M., Petri, A., Obad, S., Lindholm, M., Hedtjärn, M., Hansen, H. F., Berger, U., et al. (2008) · Nature · doi:10.1038/nature06783 · Cited by 1,589
BASKERVILLE, S., & BARTEL, D. P. (2005) · RNA · doi:10.1261/rna.7240905 · Cited by 1,508
Small non-coding RNAs in animal development
Stefani, G., & Slack, F. J. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2347 · Cited by 1,390
Role of cholesterol and lipid organization in disease
Maxfield, F. R., & Tabas, I. A. (2005) · Nature · doi:10.1038/nature04399 · Cited by 1,331
MicroRNAs in Cancer: Small Molecules With a Huge Impact
Iorio, M. V., & Croce, C. M. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.24.0317 · Cited by 973
Processing of intronic microRNAs
Kim, Y., & Kim, V. N. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601512 · Cited by 754
Elmén, J., Lindow, M., Silahtaroglu, A., Bak, M., Christensen, M., Lind-Thomsen, A., Hedtjärn, M., Hansen, J. B., Hansen, H. F., Straarup, E. M., et al. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm1113 · Cited by 683
Metabolic Syndrome: A Clinical and Molecular Perspective
Moller, D. E., & Kaufman, K. D. (2004) · Annual Review of Medicine · doi:10.1146/annurev.med.56.082103.104751 · Cited by 636
The role of reverse cholesterol transport in animals and humans and relationship to atherosclerosis
Rader, D. J., Alexander, E. T., Weibel, G. L., Billheimer, J. T., & Rothblat, G. H. (2008) · Journal of Lipid Research · doi:10.1194/jlr.r800088-jlr200 · Cited by 597
Macrophage ABCA1 and ABCG1, but not SR-BI, promote macrophage reverse cholesterol transport in vivo
Wang, X., Collins, H. L., Ranalletta, M., Fuki, I. V., Billheimer, J. T., Rothblat, G. H., Tall, A. R., & Rader, D. J. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32057 · Cited by 593
HDL, ABC transporters, and cholesterol efflux: implications for the treatment of atherosclerosis
Tall, A. R., Yvan-Charvet, L., Terasaka, N., Pagler, T., & Wang, N. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.03.001 · Cited by 540
Cholesterol feedback: from Schoenheimer's bottle to Scap's MELADL
Brown, M. S., & Goldstein, J. L. (2009) · Journal of Lipid Research · doi:10.1194/jlr.r800054-jlr200 · Cited by 441
MicroRNAs: A new class of regulatory genes affecting metabolism
Krützfeldt, J., & Stoffel, M. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.05.009 · Cited by 416
An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis
Yang, F., Vought, B. W., Satterlee, J. S., Walker, A. K., Jim Sun, Z.-Y., Watts, J. L., DeBeaumont, R., Mako Saito, R., Hyberts, S. G., Yang, S., et al. (2006) · Nature · doi:10.1038/nature04942 · Cited by 405
Self-citationde la Llera-Moya, M., Drazul‐Schrader, D., Asztalos, B. F., Cuchel, M., Rader, D. J., & Rothblat, G. H. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.109.199158 · Cited by 385
MicroRNA control of muscle development and disease
Williams, A. H., Liu, N., van Rooij, E., & Olson, E. N. (2009) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.01.029 · Cited by 347
Increased ABCA1 activity protects against atherosclerosis
Singaraja, R. R., Fievet, C., Castro, G., James, E. R., Hennuyer, N., Clee, S. M., Bissada, N., Choy, J. C., Fruchart, J.-C., McManus, B. M., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15748 · Cited by 250
Osborne, T. F., & Espenshade, P. J. (2009) · Genes & Development · doi:10.1101/gad.1854309 · Cited by 238
Eck, M. V., Singaraja, R. R., Ye, D., Hildebrand, R. B., James, E. R., Hayden, M. R., & van Berkel, T. J. C. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000208364.22732.16 · Cited by 170
Molecular regulation of macrophage reverse cholesterol transport
Wang, X., & Rader, D. J. (2007) · Current Opinion in Cardiology · doi:10.1097/hco.0b013e3281ec5113 · Cited by 112
Cepred: Predicting the Co-Expression Patterns of the Human Intronic microRNAs with Their Host Genes
Wang, D., Lü, M., Miao, J., Li, T., Wang, E., & Cui, Q. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004421 · Cited by 54
Flagged first, then by citations
1 of the 31 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- 10.1172/jci0215748 · DOI · Paper page
Cited by
Sorted by citations
Mechanisms and regulation of cholesterol homeostasis
Luo, J., Yang, H., & Song, B.-L. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0190-7 · Cited by 1,980
MicroRNAs in Stress Signaling and Human Disease
Mendell, J. T., & Olson, E. N. (2012) · Cell · doi:10.1016/j.cell.2012.02.005 · Cited by 1,673
Hammond, S. M. (2015) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.05.001 · Cited by 1,324
MicroRNA: Function, Detection, and Bioanalysis
Dong, H., Lei, J., Ding, L., Wen, Y., Ju, H., & Zhang, X. (2013) · Chemical Reviews · doi:10.1021/cr300362f · Cited by 1,236
Pervasive roles of microRNAs in cardiovascular biology
Small, E. M., & Olson, E. N. (2011) · Nature · doi:10.1038/nature09783 · Cited by 1,180
Metadata
- Authors
- Najafi-Shoushtari, S. H., Kristo, F., Li, Y., Shioda, T., Cohen, D. E., Gerszten, R. E., & Näär, A. M.
- Affiliations
- Harvard University (US)
- Massachusetts General Hospital (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Näär, Anders M.
- ORCID
- Venue
- Science
- Published
- 2010-06-18
- Volume
- 328
- Issue
- 5985
- Pages
- 1566-1569
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3840500
- OpenAlex
- W2102901373
- Semantic Scholar
- 8e1f87e5a8c468d11cb938b52c20c8e6954402ce
- Cited by
- 957
- References
- 31
- Citations by year
- 2026: 20 · 2025: 30 · 2024: 24 · 2023: 47 · 2022: 41 · 2021: 56 · 2020: 50 · 2019: 65 · 2018: 66 · 2017: 59 · 2016: 86 · 2015: 88 · 2014: 85 · 2013: 92 · 2012: 73
- FWCI
- 80.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM071449)
- National Institute of Diabetes and Digestive and Kidney Diseases (R21DK084459, R01 DK48873, P30-DK34854, R01DK056626, R01 DK56626, R37DK048873, P30DK034854, R01DK048873)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- miR-33, cholesterol homeostasis, ABCA1, reverse cholesterol transport, HDL synthesis, cholesterol efflux, post-transcriptional regulation, antisense oligonucleotides, locked nucleic acid, cholesterol biosynthesis, cardiometabolic disease
- MeSH terms
- Animals, Cell Line, Cholesterol, Diet, Gene Expression Regulation, Homeostasis, Humans, Introns, Cholesterol, HDL, Liver, Macrophages, Mice, Inbred C57BL, Up-Regulation, Oligonucleotides, Antisense, ATP-Binding Cassette Transporters, 3' Untranslated Regions, RNA Interference, MicroRNAs, Mice, Sterol Regulatory Element Binding Proteins, Sterol Regulatory Element Binding Protein 1, Sterol Regulatory Element Binding Protein 2, ATP Binding Cassette Transporter 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
