miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression
Open accessAbstract
ATP-binding cassette transporter A1 (ABCA1) is a cholesterol transporter that transfers excess cellular cholesterol onto lipid-poor apolipoproteins. Given its critical role in cholesterol homeostasis, ABCA1 has been studied as a therapeutic target for Alzheimer's disease. Transcriptional regulation of ABCA1 by liver X receptor has been well characterized. However, whether ABCA1 expression is regulated at the posttranscriptional level is largely unknown. Identification of a novel pathway that regulates ABCA1 expression may provide new strategy for regulating cholesterol metabolism and amyloid β (Aβ) levels. Since ABCA1 has an unusually long 3' untranslated region, we investigated whether microRNAs could regulate ABCA1 expression. We identified miR-106b as a novel regulator of ABCA1 expression and Aβ metabolism. miR-106b significantly decreased ABCA1 levels and impaired cellular cholesterol efflux in neuronal cells. Furthermore, miR-106b dramatically increased levels of secreted Aβ by increasing Aβ production and preventing Aβ clearance. Alterations in Aβ production and clearance were rescued by expression of miR-106b-resistant ABCA1. Taken together, our data suggest that miR-106b affects Aβ metabolism by suppressing ABCA1 expression.
AI snapshot
Written from the paper’s full text.
TL;DR
miR-106b directly represses ABCA1 translation via the ABCA1 3′ UTR, reducing cholesterol efflux and increasing secreted Aβ in neuronal cells. The Aβ increase reflects both enhanced APP processing toward Aβ production and impaired Aβ clearance, and both are rescued by miR-106b-resistant ABCA1.
Key findings
- miR-106b significantly decreased ABCA1 protein levels by approximately 45% in Neuro2a cells, 40% in HepG2 cells, and 60% in rat primary hippocampal neurons, without affecting ABCA1 mRNA levels; it also reduced luciferase activity from a full-length human ABCA1 3′ UTR reporter.
- miR-106b impaired apoA-I-mediated cholesterol efflux under basal conditions and with LXR agonist T0901317, and reduced FBS-mediated efflux without T0901317 but not with T0901317.
- miR-106b significantly increased secreted Aβ and CTFβ without changing cellular APP or BACE1 levels; miR-106b-resistant ABCA1 ORF rescued the increases in Aβ and CTFβ.
- miR-106b significantly reduced Aβ clearance in the presence of FBS, and this was rescued by miR-106b-resistant ABCA1 ORF; without FBS, miR-106b did not affect Aβ clearance. Separately, miR-106b decreased endogenous APP by ~40% (control 100±4.285% vs miR-106b 59.92±7.252%, p=0.0031, n=4).
Methods
- Cell models: mouse neuroblastoma Neuro2a cells, human hepatocyte HepG2 cells, and E18–E19 rat primary hippocampal neurons; transient transfections with synthetic miR-106b, scrambled control, miR-106b inhibitor, APPsw, and ABCA1 ORF constructs.
- Assays: qRT-PCR for ABCA1 mRNA; dual-luciferase reporter containing the full-length human ABCA1 3′ UTR; immunocytochemistry and MetaMorph quantification in primary neurons; 3H-cholesterol efflux to apoA-I or FBS; Western blot for ABCA1, APP, BACE1, CTFβ, and Aβ; Aβ secretion and Aβ40 clearance assays.
- Statistics: normality and equal variance tests followed by two-tailed Student’s t-test; data shown as mean ± SEM; significance thresholds *p<0.05, p<0.01, *p<0.001.
Limitations
- The paper states that it cannot address whether the reduction of miR-106b observed in AD cases is detrimental or beneficial, and that in vivo significance will need further study using animal models.
- The paper states that the mechanism underlying altered Aβ clearance by miR-106b remains unclear and that further studies are warranted.
- Evident from the text: the main findings are from cultured cells, with no in vivo manipulation of miR-106b; Aβ production experiments used an APP construct lacking its 3′ UTR to avoid APP-targeting confounds, and Aβ clearance impairment was FBS-dependent.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
25 of 53 cited sources checked · 11 supported · 0 flagged · accuracy not yet measured
- Premisecitation
ABCA1 has a critical role in Aβ metabolism and accumulation.
“Several lines of data strongly support that ABCA1 has a critical role in Aβ metabolism and accumulation.”
Quote in the paperSubstantial claim1 of 3 sources checked - Premisecitation
Most studies demonstrated that ABCA1 induction decreases the levels of Aβ and CTFβ.
“Most of studies demonstrated that ABCA1 induction decreases the levels of Aβ and CTFβ (Kim et al., 2007; Koldamova et al., 2003; Sun et al., 2003).”
Quote in the paperSubstantial claim2 of 3 sources checked- cites Kim et al., 2007 source
In “Regulation of Aβ Peptide Generation by ABCG1” (page unavailable), the paper reports that ABCA1 expression reduced Aβ generation by 55% in CHO-APP cells. It does not report a decrease in CTFβ, so it supports only the Aβ portion of the claim. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites Koldamova et al., 2003 source
In the Results section on APP processing (page unavailable), 22R and RA increased ABCA1 expression and reduced Aβ secretion and total APP C-terminal fragments in APPsw-expressing cells. The paper measures total CTF, not CTFβ specifically, and its Discussion says the effects on APP processing may involve factors beyond ABCA1-mediated cholesterol efflux. It therefore does not establish that ABCA1 induction itself decreases both Aβ and CTFβ. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites Sun et al., 2003 source
- Premisecitation
Overexpression of ABCA1 reduces Aβ deposition in AD mouse models.
“Genetic studies with AD mouse models have demonstrated that the deletion of ABCA1 increases Aβ deposition, while overexpression of ABCA1 dramatically reduces Aβ deposition (Hirsch-Reinshagen et al., 2004; Koldamova et al., 2005; Wahrle et al., 2005; Wahrle et al., 2008; Wahrle et al., 2004).”
Quote in the paperSubstantial claim1 of 3 sources checked- cites Hirsch-Reinshagen et al., 2004 source
- cites Koldamova et al., 2005 source
- cites Wahrle et al., 2005 source
The Discussion (page unavailable) predicts that increasing ABCA1 might decrease amyloid deposition, but explicitly says this hypothesis needs to be tested directly. The paper studies ABCA1 deletion, not overexpression, so it does not establish the claimed reduction or its magnitude. (LLM, conf=0.88)
Experimental — accuracy not yet measured
- Premisecitation
Deletion of ABCA1 increases Aβ deposition in AD mouse models.
“Genetic studies with AD mouse models have demonstrated that the deletion of ABCA1 increases Aβ deposition, while overexpression of ABCA1 dramatically reduces Aβ deposition (Hirsch-Reinshagen et al., 2004; Koldamova et al., 2005; Wahrle et al., 2005; Wahrle et al., 2008; Wahrle et al., 2004).”
Quote in the paperSubstantial claim1 of 3 sources checked
- Premisecitation
ABCA1 induction by LXR agonist decreases Aβ production in various cell lines.
“ABCA1 induction by liver X receptor (LXR) agonist decreased Aβ production in various cell lines (Kim et al., 2007; Koldamova et al., 2003; Sun et al., 2003).”
Quote in the paperSubstantial claim2 of 3 sources checked- cites Kim et al., 2007 source
The Results section reports that ABCA1 transfection reduced Aβ generation in CHO-APP cells. The Discussion also describes a previous CHO-cell study in which an LXR agonist induced ABCA1 expression and apoA-I inhibited Aβ generation. This paper does not establish that LXR-agonist induction decreased Aβ production across various cell lines. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites Koldamova et al., 2003 source
The Abstract and the results on CHOAPPsw and H4APPsw cells report reduced Aβ secretion after LXR/RXR ligand treatment, alongside increased ABCA1 expression. The claim omits that the experiments used both LXR and RXR ligands and studied cells expressing mutant APP; the larger Aβ reductions were observed with added apoA-I. The paper does not establish that ABCA1 induction alone caused the decrease. (LLM, conf=0.85)
Experimental — accuracy not yet measured - cites Sun et al., 2003 source
- Premisecitation
ABCA1 deficiency leads to an increase in Aβ and amyloid deposition.
“ABCA1 deficiency leads to an increase in Aβ and amyloid deposition (Hirsch-Reinshagen et al., 2005; Koldamova et al., 2005; Wahrle et al., 2005)”
Quote in the paperSubstantial claim2 of 3 sources checked- cites Hirsch-Reinshagen et al., 2005 source
The Results sections report increased Aβ and amyloid deposition in ABCA1-deficient Tg-SwDI/B mice. But the Abstract states that soluble and guanidine-extractable Aβ levels were unchanged in both mouse models, and Aβ deposits did not significantly increase in APP/PS1 mice. The claim omits these distinctions; page numbers were not available in the supplied copy. (LLM, conf=0.90)
Experimental — accuracy not yet measured - cites Koldamova et al., 2005 source
- cites Wahrle et al., 2005 source
- Premisecitation
Modulation of ABCA1 affects Aβ levels and amyloid accumulation in vivo.
“We and others demonstrated that modulation of ABCA1 affects Aβ levels and amyloid accumulation in vivo.”
Quote in the paperSubstantial claim2 of 3 sources checked- cites Hirsch-Reinshagen et al., 2005 source
The Discussion reports increased amyloid deposition in one of this paper’s mouse models and describes other in vivo studies that found elevated Aβ levels with ABCA1 deficiency. But this paper found no significant change in Aβ levels in either of its models, so it does not demonstrate that ABCA1 modulation affected both outcomes in its own experiments. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites Koldamova et al., 2005 source
- cites Wahrle et al., 2005 source
- Findingcitation
miR-106b was predicted to have a binding site at the near end of the 3' UTR of ABCA1 with an 8mer perfect match.
“miR-106b was predicted to have a binding site at the near end of 3′ UTR of ABCA1 with an 8mer perfect match (an exact match to positions 2–8 of the mature miRNA followed by an adenosine nucleotide) (Fig. 1A) (Bartel, 2009).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Bartel, 2009 source
The ‘Seeds of miRNA target prediction’ section (page not provided) describes predicted 8-nt seed-match sites, and ‘The influence of UTR context’ says sites near UTR ends can be more effective. Neither passage identifies an 8mer site for miR-106b in the ABCA1 3′ UTR, so the specific prediction is not supported by this source. (LLM, conf=0.87)
Experimental — accuracy not yet measured
- Premisecitation
miR-106b levels were significantly decreased in brains of AD cases and AD mouse model.
“Interestingly, miR-106b levels were significantly decreased in brains of AD cases and AD mouse model (Hebert et al., 2009; Wang et al., 2011; Wang et al., 2009).”
Quote in the paperSubstantial claim1 of 3 sources checked- cites Hebert et al., 2009 source
- cites Wang et al., 2011 source
The Results and Discussion describe downregulation of other miRNAs in human AD gray matter, but the passages found do not report decreased miR-106b. Searches for miR-106b and for decreased levels in an AD mouse model found no passage addressing either part of the claim. (LLM, conf=0.76)
Experimental — accuracy not yet measured - cites Wang et al., 2009 source
- Findingown data
Increases of Aβ levels by miR-106b were rescued by miR-106b-resistant ABCA1 ORF.
“Increases of Aβ and CTFβ levels by miR-106b were rescued by miR-106b-resistant ABCA1 ORF (Fig. 5C, 5D).”
Quote in the paperSubstantial claim - Findingown data
miR-106b dramatically represses LXR-mediated ABCA1 induction.
“While activation of LXR considerably increased ABCA1 protein levels compared with no T0901317 treatment, miR-106b dramatically repressed LXR-mediated ABCA1 induction (Fig. 3B).”
Quote in the paperSubstantial claim - Findingown data
miR-106b increases Aβ production.
“Furthermore, miR-106b dramatically increased levels of secreted Aβ by increasing Aβ production and preventing Aβ clearance.”
Quote in the paperSubstantial claim - Findingown data
miR-106b significantly attenuates cholesterol efflux to apoA-I in Neuro2a cells in the presence of LXR agonist T0901317.
“Transfection of Neuro2a cells with miR-106b significantly attenuated cholesterol efflux to apoA-I (Fig. 3A).”
Quote in the paperSubstantial claim - Findingown data
Cholesterol efflux with FBS is approximately four-fold higher than with apoA-I.
“Approximately four-fold increase in cholesterol efflux was observed with FBS (Fig. 3C) in the absence and presence of T0901317, compared with using apoA-I as an acceptor (Fig. 3A).”
Quote in the paperNot a substantial claim - Findingown data
miR-106b increases levels of secreted Aβ.
“Furthermore, miR-106b dramatically increased levels of secreted Aβ by increasing Aβ production and preventing Aβ clearance.”
Quote in the paperSubstantial claim - Findingown data
miR-106b significantly decreased ABCA1 protein levels.
“While miR-106b significantly decreased ABCA1 protein levels (Fig. 1)”
Quote in the paperSubstantial claim - Findingown data
miR-106b seed region is well conserved among mammals, such as human, rat, and mouse.
“Furthermore, miR-106b seed region was well conserved among mammals, such as human, rat, and mouse (Fig. 1A).”
Quote in the paperNot a substantial claim - Findingown data
LXR activation considerably increases ABCA1 protein levels compared with no T0901317 treatment.
“While activation of LXR considerably increased ABCA1 protein levels compared with no T0901317 treatment, miR-106b dramatically repressed LXR-mediated ABCA1 induction (Fig. 3B).”
Quote in the paperSubstantial claim - Findingown data
When Aβ clearance assay was performed without FBS, miR-106b did not affect Aβ clearance.
“when we performed Aβ clearance assay without FBS in the cell culture media, miR-106b did not affect Aβ clearance (Fig. 6E, 6F).”
Quote in the paperSubstantial claim - Findingown data
miR-106b significantly decreased cholesterol efflux.
“and cholesterol efflux (Fig. 3)”
Quote in the paperSubstantial claim - Findingown data
Alterations in Aβ production and clearance caused by miR-106b are rescued by expression of miR-106b-resistant ABCA1.
“Alterations in Aβ production and clearance were rescued by expression of miR-106b-resistant ABCA1.”
Quote in the paperSubstantial claim - Findingown data
miR-106b significantly reduces apoA-I-mediated cholesterol efflux in Neuro2a cells under basal conditions (without LXR agonist induction).
“miR-106b significantly reduced apoA-I-mediated cholesterol efflux under basal conditions (without an induction of ABCA1 gene expression by LXR agonist) (Fig. 3A).”
Quote in the paperSubstantial claim - Findingown data
Increases of CTFβ levels by miR-106b were rescued by miR-106b-resistant ABCA1 ORF.
“Increases of Aβ and CTFβ levels by miR-106b were rescued by miR-106b-resistant ABCA1 ORF (Fig. 5C, 5D).”
Quote in the paperSubstantial claim - Findingown data
miR-106b-resistant ABCA1 ORF was able to rescue the impaired Aβ clearance.
“miR-106b-resistant ABCA1 ORF was able to rescue the impaired Aβ clearance (Fig. 6C, 6D).”
Quote in the paperSubstantial claim - Findingown data
miR-106b decreases ABCA1 protein levels in rat primary hippocampal neurons by approximately 60%.
“Compared to scrambled negative control (Fig. 2A), miR-106b dramatically decreased ABCA1 levels in primary hippocampal neurons (Fig. 2B).”
- Also stated in: § Identification of miR-106b as a regulator of ABCA1 expression · hedged
“Quantitative analysis using MetaMorph® indicated approximately 60% reduction in ABCA1 protein levels by miR-106b (Fig. 2C).”
Quote in the paperSubstantial claim - Also stated in: § Identification of miR-106b as a regulator of ABCA1 expression · hedged
- Findingown data
The levels of cellular APP and BACE1 proteins were not altered by ABCA1 ORF.
“The levels of cellular APP and BACE1 proteins were not altered by ABCA1 ORF (Fig. 5A, 5B).”
Quote in the paperSubstantial claim - Findingown data
miR-106b significantly increased CTFβ, the cleavage product of APP by β-secretase.
“miR-106b significantly increased CTFβ, the cleavage product of APP by β-secretase.”
Quote in the paperSubstantial claim - Findingown data
miR-106b significantly reduces luciferase activity from a reporter containing the full-length human ABCA1 3' UTR.
“Compared to control, miR-106b significantly reduced luciferase activity (Fig. 1E).”
Quote in the paperSubstantial claim - Findingown data
FBS-mediated cholesterol efflux is not significantly suppressed by miR-106b in the presence of T0901317.
“However, FBS-mediated cholesterol efflux was not significantly suppressed by miR-106b in the presence of T0901317.”
Quote in the paperNot a substantial claim - Findingown data
miR-106b significantly reduces cholesterol efflux to FBS in the absence of LXR activation.
“miR-106b significantly reduced cholesterol efflux to FBS in the absence of LXR activation (Fig. 3C).”
Quote in the paperSubstantial claim - Findingown data
Expression of miR-106b-resistant ABCA1 significantly decreased the levels of secreted Aβ in the media, compared with empty vector.
“Expression of the miR-106b-resistant ABCA1 significantly decreased the levels of secreted Aβ in the media, compared with an empty vector transfection (Fig. 5A, 5B).”
Quote in the paperSubstantial claim - Findingown data
CTFβ levels were decreased by expression of ABCA1 ORF.
“CTFβ levels were also decreased by the expression of ABCA1 ORF.”
Quote in the paperSubstantial claim - Findingown data
miR-106b prevents Aβ clearance.
“Furthermore, miR-106b dramatically increased levels of secreted Aβ by increasing Aβ production and preventing Aβ clearance.”
Quote in the paperSubstantial claim - Findingown data
miR-106b significantly increased the levels of secreted Aβ, compared to negative control.
“miR-106b significantly increased the levels of secreted Aβ, compared to negative control (Fig. 4B).”
Quote in the paperSubstantial claim - Findingown data
miR-106b has no effect on ABCA1 mRNA level.
“miR-106b had no effect on ABCA1 mRNA level (Fig. 1D).”
Quote in the paperSubstantial claim - Findingown data
miR-106b significantly reduced Aβ clearance, compared to negative control.
“miR-106b significantly reduced Aβ clearance, compared to the negative control (Fig. 6A, 6B).”
Quote in the paperSubstantial claim - Findingown data
ABCA1 is a novel target of miR-106b.
“In the current study, we identified ABCA1 as a novel target of miR-106b.”
Quote in the paperSubstantial claim - Findingown data
miR-106b significantly decreased mouse endogenous APP levels by ~40% in Neuro2a cells.
“miR-106b significantly decreased APP levels by ~40% (Scrambled negative control: 100±4.285 % versus miR-106b: 59.92±7.252 %, p=0.0031, n=4).”
Quote in the paperSubstantial claim - Findingown data
We failed to detect an increase of Aβ clearance by ABCA1 overexpression.
“In line with previous studies, we also failed to detect an increase of Aβ clearance by ABCA1 overexpression (data not shown).”
Quote in the paperSubstantial claim - Interpretationown data
miR-106b affects Aβ metabolism by suppressing ABCA1 expression.
“Taken together, our data suggest that miR-106b affects Aβ metabolism by suppressing ABCA1 expression.”
- Also stated in: § Introduction · plain
“In this study, we identified that miR-106b functions as a novel regulator of Aβ production and clearance through the suppression of ABCA1 expression.”
Quote in the paperSubstantial claim - Also stated in: § Introduction · plain
- Interpretationown data
miR-106b suppresses ABCA1 expression in cells derived from human, rat, and mouse.
“Taken together, our data demonstrate that miR-106b suppresses ABCA1 expression in cells derived from human, rat, and mouse.”
Quote in the paperSubstantial claim - Interpretationown data
An increase of Aβ levels by miR-106b may be due to a facilitation of APP processing toward Aβ production.
“These data suggest that an increase of Aβ levels by miR-106b may be due to a facilitation of APP processing toward Aβ production.”
Quote in the paperSubstantial claim - Interpretationown data
The decrease of Aβ clearance by miR-106b is likely mediated through a repression of ABCA1.
“Collectively, our results suggest that the decrease of Aβ clearance by miR-106b is likely mediated through a repression of ABCA1”
Quote in the paperSubstantial claim - Interpretationown data
miR-106b may act by interfering with translation of ABCA1 mRNA, rather than inducing mRNA decay.
“These data suggest that miR-106b may act by interfering translation of ABCA1 mRNA, rather than inducing mRNA decay.”
Quote in the paperSubstantial claim - Premisecitation
Previous in vitro and in vivo studies demonstrated that ABCA1 influences Aβ levels.
“Previous in vitro and in vivo studies demonstrated that ABCA1 influences Aβ levels (Bu, 2009; Fan et al., 2009; Hirsch-Reinshagen and Wellington, 2007; Kim et al., 2009; Koldamova and Lefterov, 2007).”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationreasoning
Given the miR-106b-mediated alteration in APP processing, increased Aβ production appears to be responsible for the increase of extracellular Aβ levels by miR-106b.
“Given the miR-106b-mediated alteration in APP processing (Fig. 4), increased Aβ production appears to be responsible for the increase of extracellular Aβ levels by miR-106b.”
Quote in the paperSubstantial claim - Interpretationown data
ABCA1-mediated Aβ clearance depends on the presence of FBS.
“and ABCA1-mediated Aβ clearance depends on the presence of FBS.”
Quote in the paperSubstantial claim - Interpretationown data
Reduction of ABCA1 by miR-106b is sufficient to impair cellular cholesterol efflux.
“Taken together, these data demonstrate that the reduction of ABCA1 by miR-106b is sufficient to impair cellular cholesterol efflux.”
Quote in the paperSubstantial claim - Interpretationown data
The increase of Aβ by miR-106b is likely due to a repression of ABCA1, rather than other targets.
“These results suggest that the increase of Aβ by miR-106b is likely due to a repression of ABCA1, rather than other targets.”
Quote in the paperSubstantial claim- Rests on an assumption: Expression of miR-106b-resistant ABCA1 ORF does not affect other miR-106b target genes that could influence Aβ levels.
- Premisecitation
APP is another miR-106b target gene.
“Most interestingly, APP is another miR-106b target gene.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Hebert et al., 2009 source
- Interpretationown data
Our study identified a novel miRNA that regulates Aβ metabolism.
“In conclusion, our study identified a novel miRNA that regulates Aβ metabolism”
Quote in the paperSubstantial claim - Interpretationcitation
ABCA1 may affect Aβ clearance by facilitating apoE lipidation.
“This finding suggests that ABCA1 may affect Aβ clearance by facilitating apoE lipidation.”
Quote in the paperSubstantial claim - Interpretationown data
miR-106b impairs extracellular Aβ clearance by decreasing ABCA1 levels.
“Interestingly, we found that miR-106b impairs extracellular Aβ clearance by decreasing ABCA1 levels.”
Quote in the paperSubstantial claim - Study design and conductreasoning
The use of an APP construct without 3′ UTR allowed exclusion of a potentially confounding contribution by miRNA-mediated APP downregulation.
“Therefore, we were able to exclude a potentially confounding contribution by miRNA-mediated APP downregulation.”
Quote in the paperSubstantial claim- Rests on an assumption: The APP construct without 3′ UTR is not regulated by miR-106b or other miRNAs.
- Classified as probably not a substantial claim. 15
- May combine two claims. 6
Classified as probably not a substantial claim.
PremisecitationMost previous studies suggested that the main mechanism by which ABCA1 affects extracellular Aβ level is through regulation of Aβ production, not through Aβ clearance.
“Most previous studies suggested that the main mechanism by which ABCA1 affects extracellular Aβ level is through regulation of Aβ production, not through Aβ clearance (Di Paolo and Kim, 2011; Hirsch-Reinshagen and Wellington, 2007).”
Quote in the paperSubstantial claim1 of 2 sources checked- cites Di Paolo and Kim, 2011 source
In “Role of cholesterol metabolism and transport in amyloidogenesis” (page unavailable), the review says cholesterol efflux controls Aβ generation and that increased ABCA1 lowers Aβ levels in cultured cells. It also discusses ApoE lipidation and intracellular cholesterol as possible explanations for findings in mice. It does not say that most previous studies identified production, rather than clearance, as the main mechanism by which ABCA1 affects extracellular Aβ. (LLM, conf=0.83)
Experimental — accuracy not yet measured - cites Hirsch-Reinshagen and Wellington, 2007 source
Classified as probably not a substantial claim.
PremisecitationA recent in vitro study demonstrated that the presence of fully lipidated apoE is required for effective degradation of Aβ in microglia.
“A recent in vitro study demonstrated that the presence of fully lipidated apoE is required for effective degradation of Aβ in microglia (Jiang et al., 2008; Terwel et al., 2011).”
Quote in the paperSubstantial claim1 of 2 sources checked- cites Jiang et al., 2008 source
- cites Terwel et al., 2011 source
In the section on ApoE-dependent microglial phagocytosis (page not supplied), Terwel et al. report their in vitro finding that ApoE supports microglial uptake of fibrillar Aβ. The same section recounts Jiang et al.’s finding that degradation of soluble Aβ in cell cultures depends on ApoE and its lipidation status. It does not demonstrate that fully lipidated ApoE is required for microglial degradation of Aβ. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Classified as probably not a substantial claim. May combine two claims.
PremisecitationABCA1 expression was increased in the hippocampus of AD cases as well as an AD mouse model.
“Recent studies reported that ABCA1 expression was increased in the hippocampus of AD cases as well as an AD mouse model (Akram et al., 2010; Kim et al., 2010).”
Quote in the paperSubstantial claim1 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThe miR-106b cluster is known to regulate stem cell proliferation and neuronal differentiation.
“In addition, the miR-106b cluster is known to regulate stem cell proliferation and neuronal differentiation (Brett et al., 2011; Li et al., 2011; Peck and Schulze, 2011).”
Quote in the paperNot a substantial claim2 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationUptake of Aβ through apolipoprotein receptors may be another Aβ clearance pathway.
“In addition, uptake of Aβ through apolipoprotein receptors may be another Aβ clearance pathway (Bu, 2009; Fuentealba et al., 2010; Kanekiyo et al., 2011).”
Quote in the paperNot a substantial claim2 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationmiR-106b targets several genes implicated in cell cycles, such as p21, E2F, TAF5-like RNA polymerase II, and PTEN.
“Previous studies have shown that miR-106b targets several genes implicated in cell cycles, such as cyclin-dependent kinase inhibitor 1A (p21), E2F transcription factor, TAF5-like RNA polymerase II, and phosphatase and tensin homolog (Ivanovska et al., 2008; Pichiorri et al., 2008; Poliseno et al., 2010; Trompeter et al., 2011).”
Quote in the paperNot a substantial claim3 of 3 sources checked- cites Ivanovska et al., 2008 source
The Results identify p21/CDKN1A as a direct miR-106b target and report other likely cell-cycle-related targets. They do not identify TAF5-like RNA polymerase II or PTEN as targets; E2F appears in the references, but the Results say previously identified single targets were not regulated in this experimental system. Because the citations are not assigned to individual genes, this source supports only part of the cited list. (LLM, conf=0.87)
Experimental — accuracy not yet measured - cites Pichiorri et al., 2008 source
The Discussion (page unavailable) reports that the miR-106b–25 cluster targets p21, supporting that part of the claim, though it does not establish the effect for miR-106b individually. It identifies E2F1 and PTEN as targets of the different miR-17–92 cluster, and the passages do not identify TAF5-like RNA polymerase II as a miR-106b target. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites Poliseno et al., 2010 source
The Results section ('Two potentially oncogenic elements—miR-106b∼25 and MCM7—are present in the same locus'; page unavailable) states that all three members of the cluster, including miR-106b, target PTEN. The cited paper does not establish the sentence’s other listed targets—p21, E2F, or TAF5-like RNA polymerase II—so it supports only the PTEN portion of the claim. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationLevels of ABCA1 highly correlated with severity of cognitive impairment.
“levels of ABCA1 highly correlated with severity of cognitive impairment (Akram et al., 2010).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Akram et al., 2010 source
Probably not a substantial claim: may not pass S3 (load-bearing).
FindingcitationFBS functions as a very efficient cholesterol acceptor.
“As reported previously (Marquart et al., 2010), FBS functioned as a very efficient cholesterol acceptor.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Marquart et al., 2010 source
May combine two claims.
Findingown datamiR-106b decreases ABCA1 protein levels in Neuro2a mouse neuronal cells and HepG2 human hepatocytes, by approximately 45% and 40%, respectively.
“miR-106b significantly decreased ABCA1 protein levels in both mouse and human cell types (Fig. 1B).”
- Also stated in: § Identification of miR-106b as a regulator of ABCA1 expression · plain
“Approximately 45% and 40 % reductions in ABCA1 protein levels were observed in Neuro2a and HepG2 cells, respectively (Fig. 1C).”
Quote in the paperSubstantial claim- Also stated in: § Identification of miR-106b as a regulator of ABCA1 expression · plain
May combine two claims.
Findingown datamiR-106b did not noticeably change the levels of cellular APP and BACE1 proteins.
“While there were no noticeable changes in the levels of cellular APP and BACE1 proteins”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
PremisecitationABCA1 is a cholesterol transporter that transfers excess cellular cholesterol onto lipid-poor apolipoproteins.
“ATP-binding cassette transporter A1 (ABCA1) is a cholesterol transporter that transfers excess cellular cholesterol onto lipid-poor apolipoproteins.”
- Also stated in: § Introduction · plain
“ATP-binding cassette transporter A1 (ABCA1), a member of the ABC transmembrane transporter family, plays an important role in cholesterol transport by transferring cholesterol and phospholipid onto lipid-poor apolipoprotein A1 (apoA-I) and apolipoprotein E (apoE) to form high-density lipoprotein (HDL) particles (Hirsch-Reinshagen et al., 2009).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Hirsch-Reinshagen et al., 2009 source
- Also stated in: § Introduction · plain
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationABCA1 is required for the beneficial effect of LXR agonist in AD mouse model.
“Recently, Donkin et al. also indicated that ABCA1 is required for the beneficial effect of LXR agonist in AD mouse model (Donkin et al., 2010).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Donkin et al., 2010 source
May combine two claims.
Interpretationown datamiR-106b directly regulates ABCA1 expression by binding to the 3' UTR of ABCA1 and repressing its translation.
“Collectively, our data suggest that miR-106b directly regulates ABCA1 expression by binding to the 3′ UTR of ABCA1 and repressing its translation.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductown dataThe data did not violate the assumptions of parametric testing (equal variance and normality).
“After confirmation that the data did not violate the assumptions of parametric testing, a two-tailed Student’s t-test was used (GraphPad Prism 5, La Jolla, CA).”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
PremisecitationmiRNAs repress translation or degrade target mRNAs by binding to target mRNAs.
“By binding to their target messenger RNAs (mRNAs), miRNAs repress translation or degrade target mRNAs (Huntzinger and Izaurralde, 2011).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Huntzinger and Izaurralde, 2011
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
Interpretationown dataReduction of ABCA1 level below a certain endogenous level leads to an impairment of Aβ clearance, whereas an increase of ABCA1 level above endogenous level does not affect Aβ clearance in neuronal cells.
“It appears that reduction of ABCA1 level below a certain endogenous level leads to an impairment of Aβ clearance, whereas an increase of ABCA1 level above endogenous level does not affect Aβ clearance in neuronal cells.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationInduction of ABCA1 in AD brains was mainly due to increased neuronal expression.
“Induction of ABCA1 in AD brains was mainly due to increased neuronal expression (Kim et al., 2010)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Kim et al., 2010 source
Classified as probably not a substantial claim.
PremisecitationIn previous study, miR-106b significantly decreased APP levels in HeLa cervical cancer cell line.
“In previous study, miR-106b significantly decreased APP levels in HeLa cervical cancer cell line (Hebert et al., 2009).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Hebert et al., 2009 source
Probably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningThe study cannot address whether the reduction of miR-106b observed in AD cases is detrimental or beneficial for AD pathogenesis.
“our study cannot address whether the reduction of miR-106b observed in AD cases is detrimental or beneficial for AD pathogenesis.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
Posttranscriptional regulation of ABCA1 is largely unknown.
“However, whether ABCA1 expression is regulated at the posttranscriptional level is largely unknown.”
The paper relies on this without support.
The exact mechanisms underlying the regulation of Aβ metabolism by ABCA1 have not been clearly described.
“However, the exact mechanisms underlying the regulation of Aβ metabolism by ABCA1 have not been clearly described.”
The paper relies on this without support.
ABCA1 gene has an unusually long 3' UTR (>3.3 kilobases).
“ABCA1 (ABCA1) gene has an unusually long 3′ UTR (> 3.3 kilobases), raising a possibility that it might be regulated by post-transcriptional regulations, such as miRNA-mediated gene repression.”
The paper relies on this without support.
Aβ peptides are generated by sequential cleavages of APP by BACE1 and γ-secretases.
“Aβ peptides are generated by sequential cleavages of amyloid precursor protein (APP) by β-site APP-cleaving enzyme1 (BACE1) and γ-secretases.”
The paper relies on this without support.
Expression of miR-106b-resistant ABCA1 ORF does not affect other miR-106b target genes that could influence Aβ levels.
“These results suggest that the increase of Aβ by miR-106b is likely due to a repression of ABCA1, rather than other targets.”
The paper relies on this without support.
The APP construct without 3′ UTR is not regulated by miR-106b or other miRNAs.
“we used an APP construct without potential miRNA target sites (3′ UTR). Therefore, we were able to exclude a potentially confounding contribution by miRNA-mediated APP downregulation.”
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?
ABCA1 decreases Aβ levels by promoting extracellular Aβ clearance in both neurons and glial cells.
“In addition to its role in A secretion, ABCA1 has been also shown to decrease A levels by promoting extracellular A clearance in both neurons and glial cells (Jiang et al., 2008;Kim et al., 2012).”
From microRNA-33 Regulates ApoE Lipidation and Amyloid-β Metabolism in the Brain (2015) · cites this paper as Kim et al., 2012
The Results section ('Impairment of Aβ clearance by miR-106b is rescued by ABCA1 ORF expression'; page unavailable) reports that restoring ABCA1 rescued impaired extracellular Aβ clearance in neuronal cells. The Discussion says ABCA1 overexpression did not increase clearance above baseline in those cells and only suggests a possible clearance mechanism in microglia. The claim therefore overstates the evidence for promoted clearance in both neurons and glial cells. (LLM, conf=0.89)
Experimental — accuracy not yet measuredABCA1 is required for the effective clearance of Aβ by neuronal and glial cells.
“we and others have shown that ABCA1 is required for the effective clearance of A by neuronal and glial cells”
From microRNA-33 Regulates ApoE Lipidation and Amyloid-β Metabolism in the Brain (2015) · cites this paper as Kim et al., 2012
The Results section ('Impairment of Aβ clearance by miR-106b is rescued by ABCA1 ORF expression'; page not provided) shows that restoring ABCA1 rescued impaired Aβ clearance in neuronal cells, but only when the medium contained FBS. The Discussion (page not provided) describes ABCA1's possible role in microglial clearance as a suggestion, not an established requirement. The claim therefore extends the neuronal-cell finding to glial cells and omits the experimental condition. (LLM, conf=0.88)
Experimental — accuracy not yet measuredApoE lipidation by ABCA1 is critical for Aβ clearance.
“ApoE lipidation by ABCA1 is critical for A clearance (Jiang et al., 2008;Kim et al., 2012).”
From microRNA-33 Regulates ApoE Lipidation and Amyloid-β Metabolism in the Brain (2015) · cites this paper as Kim et al., 2012
The Discussion reports that fully lipidated apoE is required for effective Aβ degradation in microglia and that reducing ABCA1 impaired extracellular Aβ clearance. But it says ABCA1 *may* affect clearance by facilitating apoE lipidation and that the mechanism remains unclear; it does not establish that this route is critical. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIncrease of Aβ levels by miR-106b-5p is completely rescued by a miR-106b-5p-resistant ABCA1 construct lacking the 3' UTR.
“Increase of Aβ levels by miR-106b-5p was completely rescued by the miR-106b-5p-resistant ABCA1 construct that lacks the 3’ UTR.”
From MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease (2016) · cites this paper as [116]
The Results section, “Alteration in APP processing by miR-106b is rescued by ABCA1 ORF expression” (page unavailable), reports that a miR-106b-resistant ABCA1 construct lacking the 3′ UTR rescued the increase in Aβ. It does not state that the rescue was complete, so that degree of rescue is unsupported. (LLM, conf=0.85)
Experimental — accuracy not yet measuredABCA1 is redundantly targeted by miR-106b, miR-758, and miR-33 in the brain.
“ABCA1 is redundantly targeted by miR-106b, miR-758, and miR-33 in the brain.”
From MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease (2016) · cites this paper as [116]
The Results section reports that miR-106b suppresses ABCA1 in rat primary hippocampal neurons and supports direct regulation through ABCA1’s 3′ UTR (page not available in our copy). The passages found do not establish that miR-758 or miR-33 also target ABCA1 in the brain, or that the three act redundantly. (LLM, conf=0.88)
Experimental — accuracy not yet measured
ABCA1 decreases Aβ secretion by inhibiting BACE1-mediated APP cleavage without affecting BACE1 expression in neuronal cells.
“We and others previously demonstrated that ABCA1 decreases A secretion by inhibiting BACE1-mediated APP cleavage without affecting BACE1 expression in neuronal cells (Sun et al., 2003;Kim et al., 2012).”
From microRNA-33 Regulates ApoE Lipidation and Amyloid-β Metabolism in the Brain (2015) · cites this paper as Kim et al., 2012
miR-106b-5p directly targets the 3' UTR of ABCA1 and significantly decreases ABCA1 protein level in a neuronal cell line and in fully differentiated primary hippocampal neurons.
“miR-106b-5p directly targets the 3’ UTR of ABCA1 and significantly decreases the ABCA1 protein level in a neuronal cell line as well as in fully differentiated primary hippocampal neurons [116].”
From MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease (2016) · cites this paper as [116]
miR-106b-5p increases β-secretase cleavage of APP.
“Based on APP processing analysis, it appeared that miR-106b-5p increases the β-secretase cleavage of APP.”
From MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease (2016) · cites this paper as [116]
Reduction of ABCA1 levels by miR-106b-5p is sufficient to decrease cellular cholesterol efflux and increase Aβ secretion.
“The reduction of ABCA1 levels by miR-106b-5p was sufficient to decrease cellular cholesterol efflux and increase Aβ secretion.”
From MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease (2016) · cites this paper as [116]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Cholesterol-efflux methods name a different miRNA
MinorThe cholesterol-efflux methods say cells were transfected with miR-106, while the corresponding results attribute the effect to miR-106b. The text does not clarify whether "miR-106" is shorthand or a different reagent.
“Neuro2a cells were plated in 12-well plates (1 × 106 cells/well) and transfected with either miR-106 or scrambled negative control (Insight Genomics, Falls Church, VA) for 24hr.”
“miR-106b significantly reduced apoA-I-mediated cholesterol efflux under basal conditions (without an induction of ABCA1 gene expression by LXR agonist) (Fig. 3A).”
Aβ-clearance results use inconsistent miRNA names
MinorThe clearance methods identify miR-106b as the transfected reagent, but the results describe the same clearance experiment as using miR-106.
“In order to assess the effect of miR-106b on Aβ clearance, we transfected Neuro2a cells with scrambled negative control or miR-106 and then incubated cells with exogenously added Aβ40.”
“Neuro2A cells were transfected with miR-106b or scrambled negative control.”
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“…is sufficient to impair cellular cholesterol efflux. miR-106b increases levels of secreted Aβ Previous in vitro and in vivo studies demonstrated that ABCA1 influences Aβ levels (Bu, 2009; Fan et al., 2009; Hirsch-Reinshagen and Wellington, 2007; Kim et al., 2009; Koldamova and Lefterov, 2007).”
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“…is sufficient to impair cellular cholesterol efflux. miR-106b increases levels of secreted Aβ Previous in vitro and in vivo studies demonstrated that ABCA1 influences Aβ levels (Bu, 2009; Fan et al., 2009; Hirsch-Reinshagen and Wellington, 2007; Kim et al., 2009; Koldamova and Lefterov, 2007).”
BackgroundResultAkram, A., Schmeidler, J., Katsel, P., Hof, P. R., & Haroutunian, V. (2010) · Brain Research · doi:10.1016/j.brainres.2010.01.006 · Cited by 50 · see citing works
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Increased ATP-binding cassette transporter A1 expression in Alzheimer's disease hippocampal neurons
Kim, W. S., Bhatia, S., Elliott, D. A., Agholme, L., Kågedal, K., McCann, H., Halliday, G. M., Barnham, K. J., & Garner, B. (2010) · Journal of Alzheimer's Disease · doi:10.3233/jad-2010-100324 · Cited by 40 · see citing works
A role for the cancer-associated miR-106b 25 cluster in neuronal stem cells
Peck, B., & Schulze, A. (2011) · Aging · doi:10.18632/aging.100302 · Cited by 10 · cited 1× · see citing works
“In addition, the miR-106b cluster is known to regulate stem cell proliferation and neuronal differentiation (Brett et al., 2011; Li et al., 2011; Peck and Schulze, 2011).”
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MicroRNAs in metabolism and metabolic disorders
Rottiers, V., & Näär, A. M. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3313 · Cited by 1,156 · see citing works
MicroRNA Regulation of Atherosclerosis
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Foam cell formation: A new target for fighting atherosclerosis and cardiovascular disease
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MicroRNAs in Metabolic Disease
Fernández-Hernando, C., Ramírez, C. M., Goedeke, L., & Suárez, Y. (2013) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.112.300144 · Cited by 257 · see citing works
Self-citationThe emerging role of microRNAs in Alzheimer's disease
Femminella, G. D., Ferrara, N., & Rengo, G. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00040 · Cited by 270 · see citing works
“…can also regulate the expression of the transporter ABCA1, which is involved in ApoE production Downregulated in the temporal cortex of AD patients Kim et al., 2012 MiR-146a Regulator of inflammation-related mRNA, acts as an inflammatory response repressor in the CNS “Selective” upregulation in…”
BackgroundNoncoding <scp>RNA</scp>s in disease
Lekka, E., & Hall, J. (2018) · FEBS Letters · doi:10.1002/1873-3468.13182 · Cited by 251 · see citing works
Hepatic cholesterol transport and its role in non-alcoholic fatty liver disease and atherosclerosis
Li, H., Yu, X.-H., Ou, X., Ouyang, X.-P., & Tang, C. (2021) · Progress in Lipid Research · doi:10.1016/j.plipres.2021.101109 · Cited by 230 · see citing works
Targeting Foam Cell Formation in Atherosclerosis: Therapeutic Potential of Natural Products
Wang, D., Yang, Y., Lei, Y., Tzvetkov, N. T., Liu, X., Yeung, A. W. K., Xu, S., & Atanasov, A. G. (2019) · Pharmacological Reviews · doi:10.1124/pr.118.017178 · Cited by 223 · see citing works
“…increased ABCA1 expression (Ramirez et al., 2011). miRNA-106b significantly decreased the ABCA1 levels and the cholesterol efflux in neuronal cells (Kim et al., 2012). miRNA-183 targeted the 39-UTR of ABCA1 mRNA to degrade ABCA1 mRNA in the colon cancer cells and other tumor cells (Sarver et al.,…”
BackgroundInfluentialControl of Cholesterol Metabolism and Plasma High-Density Lipoprotein Levels by microRNA-144
Ramírez, C. M., Rotllan, N., Vlassov, A. V., Dávalos, A., Li, M., Goedeke, L., Aranda, J. F., Cirera-Salinas, D., Araldi, E., Salerno, A., et al. (2013) · Circulation Research · doi:10.1161/circresaha.112.300626 · Cited by 217 · see citing works
“NAs are able to regulate ABCA1 expression in several cell lines and tissues.(19,22,23) The contribution of each in modulat-”
BackgroundInfluentialSelf-citationNeuronal dark matter: the emerging role of microRNAs in neurodegeneration
Goodall, E. F., Heath, P. R., Bandmann, O., Kirby, J., & Shaw, P. J. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00178 · Cited by 187 · see citing works
Zhang, M., Wu, J., Chen, W., Tang, S., Mo, Z., Tang, Y., Li, Y., Wang, J., Liu, X., Peng, J., et al. (2014) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2014.02.008 · Cited by 177 · see citing works
Non-coding RNAs: the new central dogma of cancer biology
Saw, P. E., Xu, X., Chen, J., & Song, E. (2020) · Science China Life Sciences · doi:10.1007/s11427-020-1700-9 · Cited by 176 · see citing works
“Glioma (Yang et al., 2018) circNRIP1 Upregulates glucose uptake and induces lactification via sponging themiR149-5p that targets AKT1 Gastric cancer (Zhang et al., 2019b) circ-ZNF609 Promotes AKT3 by targeting miR-150-5p to improve Warburg effect Hirschsprung disease (Peng et al., 2019) circRNA_103801 Associated with…”
Kim, J., Fiesel, F. C., Belmonte, K. C., Hudec, R., Wang, W.-X., Kim, C., Nelson, P. T., Springer, W., & Kim, J. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0121-4 · Cited by 163 · see citing works
Self-citationThe Role of the ATP-Binding Cassette A1 (ABCA1) in Human Disease
Jacobo‐Albavera, L., Domínguez‐Pérez, M., Medina-Leyte, D. J., González-Garrido, A., & Villarreal-Molina, M. T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041593 · Cited by 163 · see citing works
“miR-758 [50], miR-26 [51] and miR-106b [52] have also been found to repress ABCA1 and cholesterol efflux in vitro.”
BackgroundMicroRNAs in the Pathobiology and Therapy of Atherosclerosis
Laffont, B., & Rayner, K. J. (2017) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2017.01.001 · Cited by 151 · see citing works
Millan, M. J. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.03.004 · Cited by 146 · see citing works
Kim, J., Yoon, H., Basak, J., & Kim, J. (2014) · Molecules and Cells · doi:10.14348/molcells.2014.0248 · Cited by 141 · see citing works
“…several modes of apoE modulation, such as altering its expression level or status of its lipidation, are pursed as promising therapeutic targets (Bien-Ly et al., 2012; Castellano et al., 2011; Cramer et al., 2012; Kim et al., 2009b; 2011; 2012a; 2012b; Liao et al., 2014; Wahrle et al., 2008;).”
BackgroundSelf-citationMadrigal‐Matute, J., Rotllán, N., Aranda, J. F., & Fernandez-Hernando, C. F. (2013) · Current Atherosclerosis Reports · doi:10.1007/s11883-013-0322-z · Cited by 142 · see citing works
Frambach, S. J. C. M., de Haas, R., Smeitink, J. A. M., Rongen, G. A. P. J. M., Rüssel, F. G. M., & Schirris, T. J. J. (2019) · Pharmacological Reviews · doi:10.1124/pr.119.017897 · Cited by 145 · see citing works
“…Moore, 2016; Ono, 2016; Rotllan et al., 2016; Aryal et al., 2017 miR-93 ↓ He et al., 2015 miR-96 ↓ Moazzeni et al., 2017 miR-101 ↓ Zhang et al., 2015a; Aryal et al., 2017 miR-106b ↓ Kim et al., 2012; Rotllan and Fernandez-Hernando, 2012; Dávalos and Fernandez-Hernando, 2013; Goedeke et al., 2014;…”
Role of ABC Transporters in the Pathogenesis of Alzheimer’s Disease
Abuznait, A. H., & Kaddoumi, A. (2012) · ACS Chemical Neuroscience · doi:10.1021/cn300077c · Cited by 134 · see citing works
microRNA-33 Regulates ApoE Lipidation and Amyloid-β Metabolism in the Brain
Kim, J., Yoon, H., Horie, T., Burchett, J. M., Restivo, J. L., Rotllan, N., Ramírez, C. M., Verghese, P. B., Ihara, M., Hoe, H.-S., et al. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.2053-15.2015 · Cited by 128 · see citing works
“Western blots were performed as previously described (Kim et al., 2009b, 2012).”
BackgroundMethodResultInfluentialSelf-citationExtracellular Vesicle as a Source of Alzheimer’s Biomarkers: Opportunities and Challenges
Lee, S., Mankhong, S., & Kang, J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20071728 · Cited by 125 · see citing works
Self-citationThe emerging role of epigenetics in cardiovascular disease
Khalil, C. A. (2014) · Therapeutic Advances in Chronic Disease · doi:10.1177/2040622314529325 · Cited by 123 · see citing works
Regulation of High-Density Lipoprotein Metabolism
Rye, K., & Barter, P. J. (2014) · Circulation Research · doi:10.1161/circresaha.114.300632 · Cited by 121 · see citing works
XenomiRs and miRNA homeostasis in health and disease
Witwer, K. W. (2012) · RNA Biology · doi:10.4161/rna.21619 · Cited by 115 · see citing works
Mechanistic Role of MicroRNAs in Coupling Lipid Metabolism and Atherosclerosis
Novák, J., Olejníčková, V., Tkáčová, N., & Santulli, G. (2015) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-22380-3_5 · Cited by 109 · see citing works
Regulation of ABCA1 Protein Expression and Function in Hepatic and Pancreatic Islet Cells by miR-145
Kang, M. H., Zhang, L., Wijesekara, N., de Haan, W., Butland, S. L., Bhattacharjee, A., & Hayden, M. R. (2013) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.113.302004 · Cited by 104 · see citing works
miR‐186 is decreased in aged brain and suppresses <scp>BACE</scp>1 expression
Kim, J., Yoon, H., Chung, D., Brown, J. L., Belmonte, K. C., & Kim, J. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13507 · Cited by 102 · see citing works
“miR-186 suppresses BACE1 expression by directly targeting 30UTR of BACE1 mRNA To identify the direct target genes of miR-186, we first searched genes that have putative binding sites in the 30UTR of their mRNA by utilizing several miRNA-target prediction algorithms as described previously (Kim et al. 2012).”
MethodInfluentialSelf-citationExosomes and microRNAs: New potential therapeutic candidates in Alzheimer disease therapy
Iranifar, E., Seresht, B. M., Momeni, F., Fadaei, E., Mehr, M. H., Ebrahimi, Z., Rahmati, M., Kharazinejad, E., & Mirzaei, H. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27214 · Cited by 101 · see citing works
microRNAs in the onset and development of cardiovascular disease
Vickers, K. C., Rye, K., & Tabet, F. (2013) · Clinical Science · doi:10.1042/cs20130203 · Cited by 101 · see citing works
“For example, miR-155, miR-146a and miR-29a are up-regulated in patients with CAD and miR-125a decreases the secretion of inflammatory cytokines such as IL-2, IL-6 and TNF-α from oxLDL-stimulated monocyte-derived macrophages [62,142].”
BackgroundChopra, N., Wang, R., Maloney, B., Nho, K. T., Beck, J. S., Pourshafie, N., Niculescu, A. B., Saykin, A. J., Rinaldi, C., Counts, S., et al. (2020) · Molecular Psychiatry · doi:10.1038/s41380-019-0610-2 · Cited by 101 · see citing works
Noncoding RNAs and Atherosclerosis
Aryal, B. K., Rotllán, N., & Fernandez-Hernando, C. F. (2014) · Current Atherosclerosis Reports · doi:10.1007/s11883-014-0407-3 · Cited by 94 · see citing works
miR-106b inhibits tau phosphorylation at Tyr18 by targeting Fyn in a model of Alzheimer's disease
Liu, W., Zhao, J., & Lu, G. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.08.037 · Cited by 92 · see citing works
microRNA control of HDL Metabolism and Function
Rayner, K. J., & Moore, K. (2014) · Circulation Research · doi:10.1161/circresaha.114.300645 · Cited by 89 · see citing works
“where ABCA1 plays a key role in effluxing excess cholesterol to apoE, the predominant apolipoprotein in the brain.(48,80)”
MicroRNA Regulation of Cholesterol Metabolism
Rotllán, N., & Fernandez-Hernando, C. F. (2012) · Cholesterol · doi:10.1155/2012/847849 · Cited by 86 · see citing works
Exploring Biomarkers for Alzheimer’s Disease
Sharma, N. (2016) · JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH · doi:10.7860/jcdr/2016/18828.8166 · Cited by 86 · see citing works
Fernández-de Frutos, M., Galán-Chilet, I., Goedeke, L., Kim, B., Pardo-Marqués, V., Pérez-García, A., Herrero, J. I., Fernández-Hernando, C., Kim, J., & Ramírez, C. M. (2019) · Molecular and Cellular Biology · doi:10.1128/mcb.00170-19 · Cited by 82 · see citing works
Self-citationMirnas as Biomarkers of Neurodegenerative Disorders
Viswambharan, V., Thanseem, I., Vasu, M. M., Poovathinal, S. A., & Anitha, A. (2017) · Biomarkers in Medicine · doi:10.2217/bmm-2016-0242 · Cited by 74 · see citing works
Alzheimer’s disease: presence and role of microRNAs
Basavaraju, M., & de Lencastre, A. (2016) · BioMolecular Concepts · doi:10.1515/bmc-2016-0014 · Cited by 72 · see citing works
Alzheimer’s Disease and ncRNAs
Maoz, R., Garfinkel, B. P., & Soreq, H. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-53889-1_18 · Cited by 72 · see citing works
Noncoding microRNAs: small RNAs play a big role in regulation of ADME?
Yu, A., & Pan, Y. (2012) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2012.02.011 · Cited by 69 · see citing works
Danka Mohammed, C. P., Park, J. S., Nam, H. G., & Kim, K. (2017) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.01.007 · Cited by 68 · see citing works
Lai, L., Azzam, K. M., Lin, W.-C., Rai, P., Lowe, J. M., Gabor, K. A., Madenspacher, J. H., Aloor, J. J., Parks, J. S., Näär, A. M., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.723056 · Cited by 67 · see citing works
“These include miR-758 (42), miR-26 (43), miR-106b (44), miR-10b (45), miR-144 (46, 47), and miR-101 (48).”
microRNAs in Neurodegeneration: Current Findings and Potential Impacts
Sharma, S., & Lu, H. (2018) · Journal of Alzheimer’s Disease & Parkinsonism · doi:10.4172/2161-0460.1000420 · Cited by 66 · see citing works
“Inhibition of ABCA1 gene by miR106b overexpression led to an impairment of cellular cholesterol efflux and Aβ clearance [99].”
BackgroundInfluentialMicroRNA modulation of lipid metabolism and oxidative stress in cardiometabolic diseases
Aranda, J. F., Madrigal‐Matute, J., Rotllán, N., & Fernandez-Hernando, C. F. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.07.014 · Cited by 66 · see citing works
“MiR-758 and miR-106 have been shown to regulate ABCA1 expression at the posttranscriptional level in hepatocytes, macrophages, and neuronal cells [32,33].”
Micro-RNAs and High-Density Lipoprotein Metabolism
Canfrán‐Duque, A., Lin, C., Goedeke, L., Suárez, Y., & Fernandez-Hernando, C. F. (2016) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.116.307028 · Cited by 64 · see citing works
Decoding the non-coding RNAs in Alzheimer’s disease
Schönrock, N., & Götz, J. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1125-z · Cited by 60 · see citing works
“miR-106b, which is downregulated in AD, targets ABCA1 and indeed miR-106bmediated ABCA1 repression resulted in increased Ab levels by significantly reducing Ab clearance [106].”
MicroRNA Regulation of Lipid Metabolism
Flowers, E., Froelicher, E., & Aouizerat, B. (2012) · Metabolism: Clinical and Experimental · doi:10.1016/j.metabol.2012.04.009 · Cited by 63 · see citing works
Dietary lipids modulate the expression of miR-107, an miRNA that regulates the circadian system
Daimiel, L., Klett‐Mingo, M., Konstantinidou, V., Micó, V., Aranda, J. F., García, B., Martı́nez-Botas, J., Dávalos, A., Fernandez-Hernando, C. F., & Ordovás, J. M. (2014) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201400616 · Cited by 58 · see citing works
Canfrán‐Duque, A., Ramírez, C. M., Goedeke, L., Lin, C., & Fernandez-Hernando, C. F. (2014) · Cardiovascular Research · doi:10.1093/cvr/cvu140 · Cited by 58 · see citing works
Self-citationmicroRNAs in lipoprotein and lipid metabolism: from biological function to clinical application
Desgagné, V., Bouchard, L., & Guérin, R. (2016) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2016-0575 · Cited by 56 · see citing works
Deciphering Non-coding RNAs in Cardiovascular Health and Disease
Das, A., Samidurai, A., & Salloum, F. N. (2018) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2018.00073 · Cited by 56 · see citing works
“cholesterol efflux to apoA1, including miR-33 (153–155), miR758 (156), miR-26 (157), miR-106 (158), and miR-144 (159).”
ABCA7 p.G215S as potential protective factor for Alzheimer's disease
Sassi, C., Nalls, M. A., Ridge, P. G., Gibbs, J. R., Ding, J., Lupton, M. K., Troakes, C., Lunnon, K., Al‐Sarraj, S., Brown, K. S., et al. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.04.004 · Cited by 55 · see citing works
Non-coding RNAs in Lipid Metabolism
Zhang, X.-B., Price, N., & Fernández-Hernando, C. (2018) · Vascular pharmacology · doi:10.1016/j.vph.2018.06.011 · Cited by 52 · see citing works
Epigenetic-Dependent Regulation of Drug Transport and Metabolism: An Update
Kacevska, M., Ivanov, M., & Ingelman‐Sundberg, M. (2012) · Pharmacogenomics · doi:10.2217/pgs.12.119 · Cited by 53 · see citing works
Novák, J., Vašků, J. B., Kára, T., & Novák, M. (2014) · Mediators of Inflammation · doi:10.1155/2014/275867 · Cited by 52 · see citing works
Li, Q., Li, X., Wang, L., Zhang, Y., & Chen, L. (2016) · Journal of Molecular Neuroscience · doi:10.1007/s12031-016-0815-7 · Cited by 51 · see citing works
Dávalos, A., & Fernández-Hernando, C. (2013) · Pharmacological Research · doi:10.1016/j.phrs.2013.02.005 · Cited by 47 · see citing works
Choi, J., Gao, J., Kim, J., Hong, C., Kim, J., & Tontonoz, P. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aad1904 · Cited by 49 · see citing works
“Ab40monomers were prepared as previously described (56).”
MethodSelf-citationmicroRNAs: A connection between cholesterol metabolism and neurodegeneration
Goedeke, L., & Fernandez-Hernando, C. F. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.05.034 · Cited by 49 · see citing works
“…for certain genes, such as APP, which appears to be regulated by multiple miRNAs (miR-106a-5p, miR-520-5p, miR-20a-5p, miR-106a/b-5p, miR-16-5p, miR-101-3p, miR-147-5p and miR-655) (Fan et al, 2010; Kim et al, 2012; Liu et al, 2012; Long & Lahiri, 2011; Sodhi & Singh, 2013; Vilardo et al, 2010).”
BackgroundInfluentialCheng, X., Cui, X., Zheng, Y., Zhang, G., Li, P., Huang, H., Zhao, Y., Bo, X., Wang, S., Zhou, W., et al. (2013) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2013.00065 · Cited by 48 · see citing works
MiR-9-5p inhibits mitochondrial damage and oxidative stress in AD cell models by targeting GSK-3β
Liu, J., Zuo, X., Han, J., Dai, Q., Xu, H., Liu, Y., & Cui, S. (2020) · Bioscience, Biotechnology, and Biochemistry · doi:10.1080/09168451.2020.1797469 · Cited by 47 · see citing works
Liu, D., Zhao, D., Zhao, Y., Wang, Y., Zhao, Y., & Wen, C. (2019) · Current Alzheimer Research · doi:10.2174/1567205016666190503145207 · Cited by 49 · see citing works
Free radical biology in neurological manifestations: mechanisms to therapeutics interventions
Tripathi, R. S., Gupta, R. V., Sahu, M., Srivastava, D., Das, A., Ambasta, R. K., & Kumar, P. (2021) · Environmental Science and Pollution Research · doi:10.1007/s11356-021-16693-2 · Cited by 52 · see citing works
Shen, B., Zhang, L., Lian, C., Lu, C., Zhang, Y., Pan, Q., Yang, R., & Zhao, Z. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17020200 · Cited by 46 · see citing works
Role of MicroRNAs, Aptamers in Neuroinflammation and Neurodegenerative Disorders
Khan, I., Kumari, P., Fernandes, V., Khatri, D. K., & Singh, S. B. (2021) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-021-01093-4 · Cited by 48 · see citing works
RNA binding protein HuR regulates the expression of ABCA1
Ramírez, C. M., Lin, C., Abdelmohsen, K., Goedeke, L., Yoon, J., Madrigal‐Matute, J., Martı́n-Ventura, J. L., Vo, D. T., Uren, P. J., Penalva, L. O. F., et al. (2014) · Journal of Lipid Research · doi:10.1194/jlr.m044925 · Cited by 45 · see citing works
Self-citationmiRNA and cholesterol homeostasis
Jeon, T.-I., & Osborne, T. F. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2016.01.005 · Cited by 42 · see citing works
MicroRNA regulation of cholesterol metabolism
Citrin, K. M., Fernandez-Hernando, C. F., & Suárez, Y. (2021) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14566 · Cited by 44 · see citing works
Regulation of cholesterol biosynthesis and lipid metabolism: A microRNA management perspective
Bhattarai, A., Likos, E., Weyman, C. M., & Shukla, G. C. (2021) · Steroids · doi:10.1016/j.steroids.2021.108878 · Cited by 43 · see citing works
Noncoding RNAs in Regulation of Cancer Metabolic Reprogramming
Yang, D., Sun, L., Li, Z., & Gao, P. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-981-10-1498-7_7 · Cited by 42 · see citing works
Madadi, S., Schwarzenbach, H., Saidijam, M., Mahjub, R., & Soleimani, M. (2019) · Cell & Bioscience · doi:10.1186/s13578-019-0354-3 · Cited by 41 · see citing works
MicroRNAs and lipoproteins: a connection beyond atherosclerosis?
Norata, G., Sala, F., Catapano, A., & Fernández-Hernando, C. (2012) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2012.11.019 · Cited by 43 · see citing works
Diagnostic and theranostic microRNAs in the pathogenesis of atherosclerosis
Shoeibi, S. (2020) · Acta Physiologica · doi:10.1111/apha.13353 · Cited by 38 · see citing works
Li, G., Kim, C., Kim, J., Yoon, H., Zhou, H., & Kim, J. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-150024 · Cited by 39 · see citing works
Self-citationPrimate-specific miR-603 is implicated in the risk and pathogenesis of Alzheimer's disease
Zhang, C., Lu, J., Liu, B., Cui, Q., & Wang, Y. (2016) · Aging · doi:10.18632/aging.100887 · Cited by 40 · see citing works
“miR-106a, miR-106b[52]) that play multiple roles in the pathogenesis of AD, exhibit downregulated/upregulated in the brain and/or peripheral circulation of AD patients.”
BackgroundMandolini, C., Santovito, D., Marcantonio, P., Buttitta, F., Bucci, M., Ucchino, S., Mezzetti, A., & Cipollone, F. (2015) · NMCD. Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2014.09.005 · Cited by 38 · see citing works
The role of microRNAs regulatory network in Alzheimer’s disease: a bioinformatics analysis
Sun, C., Qi, X., Liu, J., Duan, F., & Cong, L. (2021) · Archives of Medical Science · doi:10.5114/aoms/80619 · Cited by 40 · see citing works
“Until now, many studies have implicated miRNAs in amyloidogenesis, especially as a central factor in AD, such as miR-7 [9, 22], miR-9 [9, 15], miR-26b [14, 30], miR-34a [31], miR-98-5p [32], miR-106 [33], miR-128 [34], miR-132 [35], miR-144 [36], miR146a [37], miR-153 [38], miR-181 [39], miR-2115p [40] and miR-339-5p…”
MicroRNA-33 in atherosclerosis etiology and pathophysiology.
Chen, W.-J., Zhang, M., Zhao, G.-J., Fu, Y., Zhang, D.-W., Zhu, H.-B., & Tang, C.-K. (2013) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2012.11.025 · Cited by 41 · see citing works
Tian, G.-P., Tang, Y., He, P., Lv, Y.-C., Ouyang, X.-P., Zhao, G., Tang, S., Wu, J., Wang, J., Peng, J., et al. (2013) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2013.11.109 · Cited by 36 · see citing works
MiR-106b exhibits an anti-angiogenic function by inhibiting STAT3 expression in endothelial cells
Maimaiti, A., Maimaiti, A., Yang, Y., et al. (2016) · Lipids in Health and Disease · doi:10.1186/s12944-016-0216-5 · Cited by 36 · see citing works
microRNA regulation of lipoprotein metabolism
Goedeke, L., Aranda, J. F., & Fernandez-Hernando, C. F. (2014) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000094 · Cited by 34 · see citing works
MicroRNA-221 may be involved in lipid metabolism in mammary epithelial cells.
Chu, M.-Q., Zhao, Y., Yu, S., Hao, Y., Zhang, P., Feng, Y.-N., Zhang, H.-F., Ma, D.-X., Liu, J., Cheng, M., et al. (2018) · International Journal of Biochemistry and Cell Biology · doi:10.1016/j.biocel.2018.02.014 · Cited by 30 · see citing works
Genomic Variants and Multilevel Regulation of ABCA1, ABCG1, and SCARB1 Expression in Atherogenesis
Rozhkova, A., Dmitrieva, V., Nosova, E., Dergunov, A., Limborska, S., & Dergunova, L. (2021) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd8120170 · Cited by 25 · see citing works
“MiR-106b directly bound to the 3′-UTR of ABCA1 and repressed its translation [163].”
BackgroundImpact of natural products on the cholesterol transporter ABCA1
Wang, D., Hiebl, V., Xu, T., Ladurner, A., Atanasov, A. G., Heiß, E. H., & Dirsch, V. M. (2019) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2019.112444 · Cited by 34 · see citing works
The effects of micro RNA on the absorption, distribution, metabolism and excretion of drugs
He, Y., Chevillet, J. R., Liu, G., Kim, T. K., & Wang, K. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12968 · Cited by 33 · see citing works
“…Dluzen et al., 2014 ABCA1 Transporter miR-33, -33*, -758, -106b, -613, -27a, -27b, -145, -101, -135b Ramirez et al., 2011; Borel et al., 2012; Kim et al., 2012; Goedeke et al., 2013; Kang et al., 2013; Rottiers et al., 2013; Zhang et al., 2014; Zhao et al., 2014 ABCB1/P-gp/MDR1 Transporter…”
Emerging Role of ABC Transporters in Glia Cells in Health and Diseases of the Central Nervous System
Villa, M., Wu, J., Hansen, S. M., & Pahnke, J. (2024) · Cells · doi:10.3390/cells13090740 · Cited by 32 · see citing works
“Some microRNAs which regulate ABCA1 have been implicated in A β accumulation (miR-106b) [206] or cholesterol metabolism (miR-758 and miR-33) [207–210].”
BackgroundMicroRNA Biomarkers in Neurodegenerative Diseases and Emerging Nano-Sensors Technology
Shah, P., Cho, S. K., Thulstrup, P. W., Bjerrum, M. J., Lee, P. H., Kang, J., Bhang, Y.-J., & Yang, S. W. (2017) · Journal of Movement Disorders · doi:10.14802/jmd.16037 · Cited by 32 · see citing works
Downregulation of serum miR-106b: a potential biomarker for Alzheimer disease
Madadi, S., Saidijam, M., Yavari, B., & Soleimani, M. (2020) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2020.1734842 · Cited by 32 · see citing works
Loh, W. P., Yang, Y., & Lam, K. (2017) · Biotechnology Journal · doi:10.1002/biot.201600488 · Cited by 32 · see citing works
MicroRNA-126 participates in lipid metabolism in mammary epithelial cells.
Chu, M.-Q., Zhao, Y., Feng, Y.-N., Zhang, H.-F., Liu, J., Cheng, M., Li, L., Shen, W., Cao, H., Li, Q., et al. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.05.039 · Cited by 28 · see citing works
“…NC inhibitor 50-CAGUACUUUUGUGUAGUACAA-30 miR-1, miR-206, miR-613, miR-146a, and miR-155 are also involved in lipid metabolism via ABCA1, liver X receptor alpha (LXRa), or other proteins (Ramirez et al., 2011; Kim et al., 2012; Sun et al., 2012a; Zhong et al., 2013a; Zhong et al., 2013b).”
BackgroundNon-Coding RNAs and Lipid Metabolism
Smolle, E., & Haybaeck, J. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms150813494 · Cited by 31 · see citing works
“Other miRNAs that play essential roles in lipid metabolism by targeting and repressing ABCA1 in various cell types are miR-106, miR-26 and miR-758 [66–68].”
BackgroundZhang, W., Shen, Z., Xing, Y., et al. (2019) · Experimental Cell Research · doi:10.1016/j.yexcr.2019.111734 · Cited by 30 · see citing works
Regulation of HDL Genes: Transcriptional, Posttranscriptional, and Posttranslational
Kardassis, D., Gafencu, A. V., Zannis, V. I., & Dávalos, A. (2014) · Handbook of experimental pharmacology · doi:10.1007/978-3-319-09665-0_3 · Cited by 30 · see citing works
“Regarding other tissues, miR-106b (Kim et al. 2012) and miR-758 (Ramirez et al. 2011) were found to regulate neuronal cholesterol excess.”
BackgroundInfluentialThe diverse roles of macrophages in metabolic inflammation and its resolution
Guha-Ray, A., Odum, O., Wiseman, D., & Weinstock, A. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1147434 · Cited by 29 · see citing works
“, 2011b), miR-106 (Kim et al., 2012), miR-128–1 (Wagschal et al.”
Abdelmaksoud, N. M., Sallam, A.-A. M., Abulsoud, A. I., El‐Dakroury, W. A., Mageed, S. S. A., AL‐Noshokaty, T. M., Elrebehy, M. A., Elshaer, S. S., Mahmoud, N. A., Fathi, D., et al. (2023) · Pathology - Research and Practice · doi:10.1016/j.prp.2023.155007 · Cited by 30 · see citing works
MicroRNAs and Lipoprotein Metabolism
Horie, T., Baba, O., Kuwabara, Y., Yokode, M., Kita, T., Kimura, T., & Ono, K. (2014) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.20859 · Cited by 29 · see citing works
The role of microRNAs in liver injury at the crossroad between hepatic cell death and regeneration
Lauschke, V. M., Mkrtchian, S., & Ingelman-Sundberg, M. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.10.084 · Cited by 29 · see citing works
Singh, D., Rai, V., & Agrawal, D. K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232213731 · Cited by 29 · see citing works
- Authors
- Kim, J., Yoon, H., Ramírez, C. M., Lee, S.-M., Hoe, H.-S., Fernández-Hernando, C., & Kim, J.
- Affiliations
- Washington University in St. Louis (US)
- Georgetown University Medical Center (US)
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 235
- Issue
- 2
- Pages
- 476-483
- ISSN
- 0014-4886 (ISSN-L)
- PMC
- PMC3328628
- OpenAlex
- W2065691532
- Cited by
- 173
- References
- 63
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 5 · 2022: 10 · 2021: 15 · 2020: 8 · 2019: 13 · 2018: 10 · 2017: 12 · 2016: 24 · 2015: 10 · 2014: 21 · 2013: 22 · 2012: 13
- FWCI
- 5.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion)
- PubMed Central (submittedVersion)
- Funders
- NIH
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- miR-106b, ABCA1, cholesterol efflux, amyloid-beta, Alzheimer's disease, microRNA regulation, post-transcriptional regulation, 3' untranslated region, cholesterol homeostasis, amyloid-beta clearance, neurons
- MeSH terms
- Animals, Biological Transport, Active, Cells, Cultured, Cholesterol, Humans, Signal Transduction, Down-Regulation, Up-Regulation, Amyloid beta-Peptides, Rats, Sprague-Dawley, ATP-Binding Cassette Transporters, MicroRNAs, Mice, Rats, Hep G2 Cells, ATP Binding Cassette Transporter 1
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