The DOI matches its Crossref record; 62 of the 63 references it cites were found in a registry or an index; 25 of the 53 sources its claims cite were checked for support.
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.
Overview
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.
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Claims the paper makes
32 Own result · 15 Own interpretation · 11 Partly supported · 6 No full text of the sources · 4 Supported so far · 2 Own method · 1 Supported · 1 Couldn’t confirm · 1 Sources not found · 1 Not checked yet · accuracy not yet measured
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Several lines of data strongly support that ABCA1 has a critical role in Aβ metabolism and accumulation.”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Introduction
What the sources say
- Supportedcites Kim et al., 2007 source
The paper reports that ABCA1 suppresses Aβ generation and concludes that it plays a significant role in regulating APP processing. The Discussion also reports that ABCA1 deletion increased Aβ deposition in most amyloidogenic mouse models examined, supporting the claim about accumulation. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites Hirsch-Reinshagen et al., 2004 source
- Not checked — no full text of the sourcecites Donkin et al., 2010 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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).”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Discussion
What the sources say
- Partly supportedcites Kim et al., 2007 sourceExperimental — accuracy not yet measured
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)
- Partly supportedcites Koldamova et al., 2003 sourceExperimental — accuracy not yet measured
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)
- Not checked — no full text of the sourcecites Sun et al., 2003 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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).”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Introduction
What the sources say
- Not checked — no full text of the sourcecites Hirsch-Reinshagen et al., 2004 source
- Not checked — no full text of the sourcecites Koldamova et al., 2005 source
- Partly supportedcites Wahrle et al., 2005 sourceExperimental — accuracy not yet measured
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)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“whereas ABCA1 overexpression ameliorated Aβ accumulation (Donkin et al., 2010; Wahrle et al., 2008).”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Discussion
What the sources say
- Not checked — no full text of the sourcecites Donkin et al., 2010 source
- Supportedcites Wahrle et al., 2008 source
The Introduction reports decreased Aβ deposition and fibrillogenesis in PDAPP mouse cohorts with at least twofold ABCA1 overexpression. This supports the claim that overexpression ameliorated Aβ accumulation, specifically deposited Aβ in that mouse model. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“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).”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Introduction
What the sources say
- Not checked — no full text of the sourcecites Hirsch-Reinshagen et al., 2004 source
- Not checked — no full text of the sourcecites Koldamova et al., 2005 source
- Supportedcites Wahrle et al., 2005 source
The Discussion states that the absence of ABCA1 increased amyloid deposition in PDAPP mice. The cited paper supports the deletion claim in this AD mouse model; the separate overexpression clause is not attributed specifically to this paper. (LLM, conf=0.94)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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).”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Introduction
What the sources say
- Partly supportedcites Kim et al., 2007 sourceExperimental — accuracy not yet measured
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)
- Partly supportedcites Koldamova et al., 2003 sourceExperimental — accuracy not yet measured
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)
- Not checked — no full text of the sourcecites Sun et al., 2003 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“ABCA1 deficiency leads to an increase in Aβ and amyloid deposition (Hirsch-Reinshagen et al., 2005; Koldamova et al., 2005; Wahrle et al., 2005)”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Discussion
What the sources say
- Partly supportedcites Hirsch-Reinshagen et al., 2005 sourceExperimental — accuracy not yet measured
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)
- Not checked — no full text of the sourcecites Koldamova et al., 2005 source
- Supportedcites Wahrle et al., 2005 source
The Aβ results section reports that 12-month-old PDAPP mice lacking Abca1 had more than threefold higher levels of insoluble Aβ40 and Aβ42 than PDAPP mice with Abca1. The Discussion states that absence of ABCA1 increased amyloid deposition in PDAPP mice. The finding is specific to this mouse model, rather than a demonstrated effect in humans. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“We and others demonstrated that modulation of ABCA1 affects Aβ levels and amyloid accumulation in vivo.”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Discussion
What the sources say
- Partly supportedcites Hirsch-Reinshagen et al., 2005 sourceExperimental — accuracy not yet measured
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)
- Not checked — no full text of the sourcecites Koldamova et al., 2005 source
- Supportedcites Wahrle et al., 2005 source
The Abstract reports that deleting Abca1 in PDAPP mice increased parenchymal Aβ levels and amyloid deposition at 12 months. This supports the claim that changing ABCA1 affects both outcomes in vivo; the demonstrated change was deletion, not increased ABCA1 activity. (LLM, conf=0.92)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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).”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Results > Identification of miR-106b as a regulator of ABCA1 expression
What the sources say
- Partly supportedcites Bartel, 2009 sourceExperimental — accuracy not yet measured
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)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“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).”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Discussion
What the sources say
- Not checked — no full text of the sourcecites Hebert et al., 2009 source
- Could not verifycites Wang et al., 2011 sourceExperimental — accuracy not yet measured
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)
- Not checked — no full text of the sourcecites Wang et al., 2009 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 15
- It may state two separate claims as one. 6
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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).”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Discussion
What the sources say
- Partly supportedcites Di Paolo and Kim, 2011 sourceExperimental — accuracy not yet measured
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)
- Not checked — no full text of the sourcecites Hirsch-Reinshagen and Wellington, 2007 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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).”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Discussion
What the sources say
- Not checked — no full text of the sourcecites Jiang et al., 2008 source
- Partly supportedcites Terwel et al., 2011 sourceExperimental — accuracy not yet measured
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)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“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).”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Discussion
What the sources say
- Supportedcites Akram et al., 2010 source
The Results (section 3.1) report greater hippocampal ABCA1 gene expression in subjects with AD than in those without AD. This citation supports the human AD-cases portion of the sentence; the mouse-model portion is accompanied by a separate citation. (LLM, conf=0.93)
- Not checked — no full text of the sourcecites Kim et al., 2010 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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).”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Discussion
What the sources say
- Supportedcites Brett et al., 2011 source
The Introduction reports that overexpressing the miR-106b~25 cluster increases proliferation in adult mouse neural stem/progenitor cells and enhances their differentiation toward the neuronal lineage. The Discussion reiterates both findings. The claim is a broad paraphrase of those results. (LLM, conf=0.94)
- Not matchedcites Li et al., 2011
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Supportedcites Peck and Schulze, 2011 source
The main text (page not supplied) reports that miR-106b~25 regulates the proliferative potential and differentiation of adult neural stem/progenitor cells. It also reports that overexpressing the cluster increased proliferation and the proportion of cells positive for a neuronal marker. Although the paper discusses Brett et al.’s study, it reports and relies on that finding. (LLM, conf=0.94)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In addition, uptake of Aβ through apolipoprotein receptors may be another Aβ clearance pathway (Bu, 2009; Fuentealba et al., 2010; Kanekiyo et al., 2011).”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Discussion
What the sources say
- Not matchedcites Bu, 2009
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Supportedcites Fuentealba et al., 2010 source
The Discussion (page not available) reports that LRP1 mediates neuronal Aβ42 uptake and that imaging suggests much of the internalized Aβ42 is degraded. This supports the hedged claim that uptake through an apolipoprotein receptor may provide an Aβ clearance pathway, although the paper also notes that Aβ42 can accumulate when degradation capacity is exceeded. (LLM, conf=0.90)
- Supportedcites Kanekiyo et al., 2011 source
The Introduction identifies LRP1 as a member of the LDL receptor family involved in Aβ clearance. The Discussion states that cellular uptake and degradation are a major Aβ clearance pathway and reports that LRP1 cooperates in neuronal Aβ uptake. The copy does not provide page numbers for these passages. (LLM, conf=0.92)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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).”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Discussion
What the sources say
- Partly supportedcites Ivanovska et al., 2008 sourceExperimental — accuracy not yet measured
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)
- Partly supportedcites Pichiorri et al., 2008 sourceExperimental — accuracy not yet measured
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)
- Partly supportedcites Poliseno et al., 2010 sourceExperimental — accuracy not yet measured
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)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“levels of ABCA1 highly correlated with severity of cognitive impairment (Akram et al., 2010).”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Discussion
What the sources say
- Supportedcites Akram et al., 2010 source
The Discussion states that hippocampal ABCA1 gene expression was strongly correlated with increasing cognitive impairment. The Results also report significant correlations between ABCA1 mRNA and protein expression and clinical dementia rating (CDR). Page numbers were not provided in our copy. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
In the paper
“As reported previously (Marquart et al., 2010), FBS functioned as a very efficient cholesterol acceptor.”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Results > miR-106b decreases cellular cholesterol efflux
What the sources say
- Not checked — no full text of the sourcecites Marquart et al., 2010 source
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Results > Identification of miR-106b as a regulator of ABCA1 expression
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Identification of miR-106b as a regulator of ABCA1 expression · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While there were no noticeable changes in the levels of cellular APP and BACE1 proteins”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Results > miR-106b increases levels of secreted Aβ
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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).”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Abstract
What the sources say
- Not checked — no full text of the sourcecites Hirsch-Reinshagen et al., 2009 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Also stated in: § Introduction · plain
In the paper
“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).”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Introduction
What the sources say
- Not checked — no full text of the sourcecites Donkin et al., 2010 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Collectively, our data suggest that miR-106b directly regulates ABCA1 expression by binding to the 3′ UTR of ABCA1 and repressing its translation.”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Results > Identification of miR-106b as a regulator of ABCA1 expression
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Materials and Methods > Statistical analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“By binding to their target messenger RNAs (mRNAs), miRNAs repress translation or degrade target mRNAs (Huntzinger and Izaurralde, 2011).”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Introduction
What the sources say
- Not matchedcites Huntzinger and Izaurralde, 2011
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Induction of ABCA1 in AD brains was mainly due to increased neuronal expression (Kim et al., 2010)”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Discussion
What the sources say
- Not checked — no full text of the sourcecites Kim et al., 2010 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In previous study, miR-106b significantly decreased APP levels in HeLa cervical cancer cell line (Hebert et al., 2009).”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Discussion
What the sources say
- Not checked — no full text of the sourcecites Hebert et al., 2009 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“our study cannot address whether the reduction of miR-106b observed in AD cases is detrimental or beneficial for AD pathogenesis.”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
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?
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
“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
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 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
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
“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
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
“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]
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
“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]
Experimental — accuracy not yet measured
The cited source says what the claim attributes to it.
In the citing paper
“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
The cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Materials and Methods > Cholesterol Efflux Assays
“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 impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Results > miR-106b decreases cellular cholesterol efflux
“miR-106b significantly reduced apoA-I-mediated cholesterol efflux under basal conditions (without an induction of ABCA1 gene expression by LXR agonist) (Fig. 3A).”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Results > Impairment of Aβ clearance by miR-106b is rescued by ABCA1 ORF expression
“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.”
§ miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression > Materials and Methods > Aβ clearance assays
“Neuro2A cells were transfected with miR-106b or scrambled negative control.”
Citations
Cites
MicroRNAs: Target Recognition and Regulatory Functions
Bartel, D. P. (2009) · Cell · doi:10.1016/j.cell.2009.01.002 · Cited by 20,068 · cited 1×
“1A) (Bartel, 2009).”
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864
Lewis, B. P., Burge, C. B., & Bartel, D. P. (2005) · Cell · doi:10.1016/j.cell.2004.12.035 · Cited by 11,855
Combinatorial microRNA target predictions
Krek, A., Grün, D., Poy, M. N., Wolf, R., Rosenberg, L., Epstein, E. J., MacMenamin, P., da Piedade, I., Gunsalus, K. C., Stoffel, M., et al. (2005) · Nature Genetics · doi:10.1038/ng1536 · Cited by 4,603
The microRNA.org resource: targets and expression
Betel, D., Wilson, M. T., Gabow, A. P., Marks, D. S., & Sander, C. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm995 · Cited by 2,530
Gene silencing by microRNAs: contributions of translational repression and mRNA decay
Huntzinger, E., & Izaurralde, E. (2011) · Nature Reviews Genetics · doi:10.1038/nrg2936 · Cited by 2,339 · cited 2×
“However, recent studies suggest that miRNA can also cause mRNA decay (Huntzinger and Izaurralde, 2011).”
BackgroundThe role of apolipoprotein E in Alzheimer's disease
Kim, J., Basak, J. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.026 · Cited by 1,661
Self-citationAlzheimer’s Disease: The Challenge of the Second Century
Holtzman, D. M., Morris, J. C., & Goate, A. M. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002369 · Cited by 1,424
MiR-33 Contributes to the Regulation of Cholesterol Homeostasis
Rayner, K. J., Suárez, Y., Dávalos, A., Parathath, S., Fitzgerald, M. L., Tamehiro, N., Fisher, E. A., Moore, K. J., & Fernández-Hernando, C. (2010) · Science · doi:10.1126/science.1189862 · Cited by 1,260
Hébert, S. S., Horré, K., Nicolaï, L., Papadopoulou, A. S., Mandemakers, W., Silahtaroglu, A. N., Kauppinen, S., Delacourte, A., & De Strooper, B. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0710263105 · Cited by 1,183
Cited by
Sorted by citations
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
MicroRNA Regulation of Atherosclerosis
Feinberg, M. W., & Moore, K. J. (2016) · Circulation Research · doi:10.1161/circresaha.115.306300 · Cited by 638
Foam cell formation: A new target for fighting atherosclerosis and cardiovascular disease
Maguire, E. M., Pearce, S. W. A., & Xiao, Q. (2018) · Vascular Pharmacology · doi:10.1016/j.vph.2018.08.002 · Cited by 380
Cheng, L., Doecke, J. D., Sharples, R. A., Villemagne, V. L., Fowler, C. J., Rembach, A., Martins, R. N., Rowe, C. C., Macaulay, S. L., Masters, C. L., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.127 · Cited by 409
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
Self-citation
Metadata
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › 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
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.
A language model drew the claims from the paper on 2026-10-17, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-17 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
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 ›
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