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Cited by 679Genetic Neurodegenerative DiseasesMicroRNA in disease regulationGenetics and Neurodevelopmental Disorders

The Bifunctional microRNA miR-9/miR-9* Regulates REST and CoREST and Is Downregulated in Huntington's Disease

Open access
Packer, Amy N., Xing, Yi, Harper, Scott Q., Jones, Lesley, Davidson, Beverly L.·2008·The Journal of Neuroscience
DOI 10.1523/jneurosci.2390-08.2008PMC PMC3124002
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Abstract

The transcription factor REST silences neuronal gene expression in non-neuronal cells. In neurons, the protein is sequestered in the cytoplasm in part through binding to huntingtin. Polyglutamine expansions in huntingtin, which causes Huntington's disease (HD), abrogates REST-huntingtin binding. Consequently, REST translocates to the nucleus, occupies RE1 repressor sequences and decreases neuronal gene expression. In this work, we found that levels of several microRNAs (miRNAs) with upstream RE1 sites are decreased in HD patient cortices relative to healthy controls. Interestingly, one of these, the bifunctional brain enriched miR-9/miR-9*, targets two components of the REST complex: miR-9 targets REST and miR-9* targets CoREST. These data provide evidence for a double negative feedback loop between the REST silencing complex and the miRNAs it regulates.

AI snapshot

Written from the paper’s full text.

TL;DR

In Huntington’s disease (HD) cortex, several REST-regulated microRNAs are downregulated with disease progression, including the bifunctional miR-9/miR-9*. The authors show that miR-9 targets REST and miR-9* targets CoREST, supporting a double-negative feedback loop between the REST silencing complex and the miRNAs it regulates.

Key findings

  • In Brodmann’s area 4 (BA4) cortex, five predicted REST-regulated miRNAs were significantly diminished with increasing HD grade: miR-9 (F(3,22)=9.876, p=0.0003), miR-9* (F(3,22)=6.799, p=0.0021), miR-29b (F(3,22)=3.658, p=0.0281), miR-124a (F(3,16)=7.833, p=0.001), and miR-132 (F(3,22)=7.611, p=0.0011).
  • A QPCR miRNA array of 365 mature miRNAs in control and early HD (grades 1 and 2) BA4 cortex found an additional 5 decreased miRNAs; miR-196a and miR-486 were increased by nearly 6-fold and 3-fold, respectively, in HD1 samples relative to controls.
  • miR-9 targets REST and miR-9* targets CoREST: pre-miR-9 reduced REST reporter and endogenous REST protein, while pre-miR-9* reduced CoREST reporter and endogenous CoREST protein; target site protectors rescued these effects.
  • Reducing REST expression in HEK 293 and NT2 cells enhanced miR-9 expression and processing (p<0.05), providing functional evidence for a negative feedback loop between the REST complex and REST-regulated miRNAs.

Methods

  • Postmortem BA4 cortex samples from healthy controls (n=7; ages 46–62) and HD grade 1 (n=7; ages 42–70), grade 2 (n=6; ages 45–78), grade 3 (n=2; ages 60–65), and grade 4 (n=4; ages 53–60); CAG repeat length was 16–21 for controls and 37–46 for HD, with postmortem time 2–20 hrs.
  • Mature miRNA expression was measured by quantitative PCR using TaqMan Array Human MiRNA Panel v1.0 or TaqMan MiRNA Assays, normalized to RNU48 and shown as fold change relative to controls.
  • Mechanistic validation used HEK 293 and NT2 cells with REST/CoREST 3′ UTR luciferase reporters, mU6 miR-9/9* or pre-miRs, anti-miRs, target site protectors, siRNAs, and Western blots; data were analyzed by one-way ANOVA with Dunnett’s post hoc analysis.

Limitations

  • The paper does not state a limitations section.
  • Evident from the text: human HD grade 3 (n=2) and grade 4 (n=4) samples were very small, and the human data are cross-sectional postmortem BA4 cortex only, limiting generalization across brain regions and disease stages.
  • Evident from the text: target validation relied heavily on HEK 293/NT2 cell lines and reporter assays rather than HD brain tissue, and the authors note it is currently under study whether diminished miRNAs result from or contribute to the dedifferentiation profile in HD cortex.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1523/jneurosci.2390-08.2008

Cites

29 of 29 references verified0 citation errors · 0 not checkable

Statistics

16 tests recomputed · 0 with the reported and recomputed p on opposite sides of .05

Claims the paper makes

2 of 45 cited sources checked · 0 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    REST mRNA levels do not change significantly in Huntington's disease.

    “This may reflect a dedifferentiation mediated by aberrant REST localization, since REST mRNA levels do not change significantly in HD (Hodges et al., 2006), as well as global changes in miR-9/9* and miR-124a target levels.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Hodges et al., 2006 source

      The ‘Regional differences and similarities in gene expression within HD brains’ section reports changes across brain regions, but does not give a result for REST mRNA. Searches for REST, NRSF, and RE1-silencing transcription factor found no passage establishing whether REST mRNA changes significantly in HD. (LLM, conf=0.74)

      Experimental — accuracy not yet measured
  • Premisecitation

    One molecular phenotype in Huntington's disease patients is transcriptional misregulation in striatum and distinct cortical regions.

    “One of the molecular phenotypes in HD patients is transcriptional misregulation in striatum and distinct cortical regions (Hodges et al., 2006).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Hodges et al., 2006 source

      The Abstract (page not provided) reports altered mRNA expression in the caudate nucleus and motor cortex of human HD brains. It also reports no detected mRNA changes in the prefrontal association cortex, so the claim overstates the evidence if “distinct cortical regions” means multiple affected cortical regions. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
  • Findingown data

    miR-218 demonstrates a trend toward increasing expression with Huntington's disease grade.

    “For miR-139, miR-135b, and miR-212 no significant differences were observed with increasing disease severity, while miR-218 demonstrated a trend toward increasing expression with disease grade (Fig. 1A).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Cotransfection of the CoREST 3' UTR reporter plasmid and 5 or 15 nM pre-miR-9* reduced reporter expression compared to controls, unlike miR-9.

    “Cotransfection of the CoREST 3′ UTR reporter plasmid and 5 or 15 nM pre-miR-9* reduced reporter expression compared to controls (F(2,11) = 41.612, p = 0.0001 and F(2,11) = 7.423, p = 0.0091, respectively), unlike miR-9, (Fig. 3A).”
    Quote in the paperSubstantial claim
  • Findingown data

    Overexpression of mU6 miR-124a or miR-132 in HEK 293 cells did not significantly reduce REST or CoREST expression.

    “Consistent with these reporter-based assays, over expression of mU6 miR-9/9*, but not mU6 miR-124a or 132, in HEK 293 cells significantly reduced REST (F(2,12) = 26.006, p = 0.0001) and CoREST (F(2,12) =24.017, p = 0.0001) expression (Fig. 1D,E).”
    Quote in the paperSubstantial claim
  • May combine two claims. 15
  • Classified as probably not a substantial claim. 16

  • May combine two claims.

    Findingown data

    REST levels in HEK 293 cells, which decreased upon mU6 miR-9/9* transfection, were rescued by TSP+ but not by a control TSP.

    “Consistent with these observations, REST levels in HEK 293 cells, which decreased upon mU6 miR-9/9* transfection (Fig. 1D,E) was rescued by TSP+ (Student t-test, p < 0.05), but not a control TSP (TSP Neg; Fig. 2D).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    miR-139, miR-135b, and miR-212 show no significant differences with increasing Huntington's disease severity.

    “For miR-139, miR-135b, and miR-212 no significant differences were observed with increasing disease severity, while miR-218 demonstrated a trend toward increasing expression with disease grade (Fig. 1A).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Endogenous CoREST protein expression, which was reduced after pre-miR-9* transfection, increased upon cotransfection of TSP+ but not TSP Neg.

    “Endogenous CoREST protein expression, which was reduced after pre-miR-9* transfection, increased upon cotransfection of TSP+ (Student t-test, p < 0.05) but not TSP Neg (Fig. 3D).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    miR-196a and miR-486 were significantly increased by nearly 6-fold and 3-fold, respectively, in HD1 samples relative to controls.

    “Also, miR-196a and miR-486 were significantly increased by nearly 6 and 3 fold respectively in HD1 samples relative to controls.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    We found no change in miR-132 at stages 1 and 2, but significant upregulation later.

    “Also, we found no change in miR-132 at stages 1 and 2, but significant upregulation later.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    We saw a trend towards increased miR-29a in tissue from early stage Huntington's disease, followed by diminished levels.

    “We saw a trend towards increased miR-29a in tissue from early stage HD, followed by diminished levels.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The 3' UTRs of REST and CoREST contain miRNA recognition elements for miR-9, miR-9*, miR-132, and miR-124a (CoREST only).

    “The 3′ UTRs of REST (Fig. S2) and CoREST (Fig. S3) contain miRNA recognition elements (MRE) for miR-9, miR-9*, miR-132 and miR-124a (CoREST only) (Wu and Xie, 2006).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Wu and Xie, 2006 source
    • cites TargetScan 4.1

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Lewis et al., 2003 source

  • May combine two claims.

    Interpretationown data

    The miR-9 predicted MREs in the 3' UTR of REST are functional, in contrast to the miR-9* predicted MREs.

    “Together, these results suggest that the miR-9 predicted MREs in the 3′ UTR of REST are functional, in contrast to the miR-9* predicted MREs.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Double negative feedback networks have been reported in other systems where critical balancing of multiple factors is essential.

    “Double negative feedback networks have been reported in other systems where critical balancing of multiple factors is essential (Tsang et al., 2007).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Tsang et al., 2007 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In zebrafish, miR-9 is important for midbrain-hindbrain boundary definition.

    “In zebrafish, miR-9 is important midbrain-hindbrain boundary definition (Leucht et al., 2008).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Leucht et al., 2008 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Over-expression of miR-124 in non-neuronal cells induces gene expression profiles to a neuronal phenotype.

    “Also, over-expression of miR-124 in non-neuronal cells induces gene expression profiles to a neuronal phenotype (Lim et al., 2005).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Lim et al., 2005 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    miR-124 promotes neuronal differentiation, in part through targeting of a splicing factor.

    “miR-124 promotes neuronal differentiation, in part through targeting of a splicing factor (Makeyev et al., 2007).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Makeyev et al., 2007 source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    miR-132 has been shown to target MeCP2, which can interact with REST and CoREST to suppress transcription.

    “MiR-132 has been shown to target MeCP2 (Klein et al., 2007), which can interact with REST and CoREST to suppress transcription (Lunyak et al., 2002).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Klein et al., 2007 source
    • cites Lunyak et al., 2002 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    REST expression is highest in pluripotent stem cells and decreases upon restriction to neural progenitor cells and subsequently to neurons.

    “REST expression is highest in pluripotent stem cells and decreases upon restriction to neural progenitor cells and subsequently to neurons (Ballas et al., 2005).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ballas et al., 2005 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In mouse cortical development, miR-9 appears necessary for appropriate differentiation of Cajal-Retzius cells.

    “In mouse cortical development, miR-9 appears necessary for appropriate differentiation of Cajal-Retzius cells (Shibata et al., 2008).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Shibata et al., 2008 source

  • May combine two claims.

    Premisecitation

    In patients with Huntington's disease, mutant Huntingtin fails to bind REST, enabling its nuclear translocation.

    “However, in patients with HD mutant Htt fails to bind REST enabling its nuclear translocation (Zuccato et al., 2003).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Zuccato et al., 2003 source

  • Classified as probably not a substantial claim.

    Premisecitation

    One putative mechanism underlying the transcriptional changes in Huntington's disease is aberrant cellular distribution of the transcriptional repressor REST.

    “One putative mechanism underlying the transcriptional changes is aberrant cellular distribution of the transcriptional repressor RE1-silencing transcription factor (REST, also known as neuronal restrictive silencing factor, NRSF) (Lunyak et al., 2002; Zuccato et al., 2003 ; Zuccato et al., 2007).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Lunyak et al., 2002 source
    • cites Zuccato et al., 2003 source
    • cites Zuccato et al., 2007 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Recent studies on brain-enriched miR-9 have revealed its importance in development and lineage commitment.

    “Recent studies on the brain enriched miR-9 have revealed its importance in development and lineage commitment (Sempere et al., 2004; Krichevsky et al., 2006).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Sempere et al., 2004 source

      Not checked in the free run.

    • cites Krichevsky et al., 2006 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Johnson and colleagues' work showed no change in miR-124a, elevated levels of miR-29a, and decreased levels of miR-132.

    “Interestingly, and in contrast to our findings, their work showed no change in miR-124a, elevated levels of miR-29a, and decreased levels of miR-132.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Johnson et al., 2008

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Premisecitation

    REST repressor complex binding to RE1 sequences upstream of miRNA transcripts may alter miRNA expression profiles.

    “Similarly, REST repressor complex binding to RE1 sequences upstream of miRNA transcripts may alter miRNA expression profiles (Conaco et al., 2006; Klein et al., 2007).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Conaco et al., 2006 source
    • cites Klein et al., 2007 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    REST can be regulated by ubiquitin-mediated proteolysis.

    “Our findings, together with recent work showing that REST can be regulated by ubiquitin-mediated proteolysis (Westbrook et al., 2008) underscore the importance of maintaining appropriate levels and intracellular localization (Zuccato et al., 2003) of this repressor complex for appropriate gene transcription and lineage commitment.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Westbrook et al., 2008 source

  • May combine two claims.

    Interpretationreasoning

    Consequently, REST translocates to the nucleus, occupies RE1 repressor sequences, and decreases neuronal gene expression.

    “Consequently, REST translocates to the nucleus, occupies RE1 repressor sequences and decreases neuronal gene expression.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Zuccato et al., 2003 source

  • Classified as probably not a substantial claim.

    Premisecitation

    REST interacts with CoREST and other transcriptional repressors to regulate neuronal gene expression and lineage commitment through its direct control of both mRNA and miRNA transcripts.

    “REST interacts with CoREST and other transcriptional repressors to regulate neuronal gene expression and lineage commitment through its direct control of both mRNA and, as shown more recently, miRNA transcripts (Vo et al., 2005; Conaco et al., 2006; Mortazavi et al., 2006 ; Visvanathan et al., 2007).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Vo et al., 2005

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Conaco et al., 2006 source
    • cites Mortazavi et al., 2006 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Previous work by Johnson and colleagues measured precursor miRNA levels in Huntington's disease brain of unknown disease grade.

    “Previous work by Johnson and colleagues measured precursor miRNA levels in HD brain of unknown disease grade (Johnson et al., 2008).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Johnson et al., 2008

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    REST is mislocalized in brains of patients with Huntington's disease, with increased nuclear localization and occupancy at RE1 sites compared to healthy controls.

    “The transcriptional repressor REST is mislocalized in brains of patients with HD, with increased nuclear localization and occupancy at RE1 sites compared to healthy controls (Zuccato et al., 2003 ; Zuccato et al., 2007).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Zuccato et al., 2003 source
    • cites Zuccato et al., 2007 source

  • May combine two claims.

    Premisecitation

    In mature, healthy neurons, REST is expressed at low levels and primarily sequestered in the cytoplasm in part through interaction with Huntingtin.

    “In mature, healthy neurons, REST is expressed at low levels and primarily sequestered in the cytoplasm in part through interaction with Htt (Zuccato et al., 2003).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Zuccato et al., 2003 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Canonical and non-canonical REST binding motifs have been mapped in close proximity to 22 miRNA sites in the human genome, including several near neuron-enriched miRNAs.

    “Indeed, canonical and non-canonical REST binding motifs have recently been mapped in close proximity to 22 miRNA sites in the human genome, including several of which are located within close proximity to neuron enriched miRNAs (Bruce et al., 2004; Jothi et al., 2008).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Bruce et al., 2004 source
    • cites Jothi et al., 2008 source

  • May combine two claims.

    Interpretationcitation

    The overrepresentation of neurogenesis-related genes among genes changed in Huntington's disease cortex may reflect a dedifferentiation mediated by aberrant REST localization, since REST mRNA levels do not change significantly in HD, as well as global changes in miR-9/9* and miR-124a target levels.

    “This may reflect a dedifferentiation mediated by aberrant REST localization, since REST mRNA levels do not change significantly in HD (Hodges et al., 2006), as well as global changes in miR-9/9* and miR-124a target levels.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Huntington's disease is caused by CAG trinucleotide repeat expansion in huntingtin, which encodes Huntingtin.

    “Huntington’s Disease (HD) is an autosomal dominant neurodegenerative disease caused by CAG trinucleotide repeat expansion in huntingtin, which encodes Huntingtin (Htt) (The Huntingtons Disease Collaborative Research Group, 1993).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites The Huntingtons Disease Collaborative Research Group, 1993

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

29 of 29

  • The paper relies on this without support.

    miR-9 and miR-9* are processed from the same primary transcript from three genomic loci (miR-9-1, 9-2, and 9-3).

    “MiR-9 and miR-9*, which decreased early in HD (Fig 1A), are processed from the same primary transcript from 3 genomic loci (miR-9-1, 9-2 and 9-3); miR-9-1 and miR-9-3 both have upstream RE1 sequences that is can be occupied by REST (Conaco et al., 2006; Johnson et al., 2008).”

  • The paper relies on this without support.

    The postmortem brain samples from Huntington's disease patients and controls are representative of the disease process and are not confounded by post-mortem interval or other factors.

    “Post-mortem time for brain samples was 2 – 20 hrs.”

  • The paper relies on this without support.

    The observed miRNA expression changes in Brodmann's area 4 cortex are attributable to Huntington's disease progression rather than to age, sex, or other demographic differences between groups.

    “Tissues were collected from Brodmann’s area 4 (BA4) cortex of healthy control (n = 7; ages 46 – 62) and HD grade 1 (n = 7; ages 42-70), 2 (n = 6; ages 45 -78), 3 (n = 2; ages 60 - 65) and 4 (n = 4; 53 - 60).”
3 of 3

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?

Statistics that don’t add up

Each reported p-value recomputed from its test statistic and degrees of freedom.

  • Inconsistent p-value: F(3,16) = 7.833, p = .001

    Minor

    The paper reports p = .001 here; recomputing from the test statistic and its degrees of freedom gives p = .002. The check cannot tell whether the statistic or the p-value is the misprint.

    Reported p = .001 · recomputed p = .002

  • Inconsistent p-value: F(2,6) = 16.134, p = .0034

    Minor

    The paper reports p = .0034 here; recomputing from the test statistic and its degrees of freedom gives p = .004. The check cannot tell whether the statistic or the p-value is the misprint.

    Reported p = .0034 · recomputed p = .004

2 of 2

Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • Doesn’t add upF(3, 16) = 7.833reported p = .001 · recomputed p = .002

    “F(3,16) = 7.833, p = .001”

  • Doesn’t add upF(2, 6) = 16.134reported p = .0034 · recomputed p = .004

    “F(2,6) = 16.134, p = .0034”

  • ConsistentF(3, 22) = 9.876reported p = .0003 · recomputed p < .001

    “F(3,22) = 9.876, p = .0003”

  • ConsistentF(3, 22) = 6.799reported p = .0021 · recomputed p = .002

    “F(3,22) = 6.799, p = .0021”

  • ConsistentF(3, 22) = 3.658reported p = .0281 · recomputed p = .028

    “F(3,22) = 3.658, p = .0281”

  • ConsistentF(2, 6) = 333.08reported p = .0001 · recomputed p < .001

    “F(2, 6) = 333.08, p = .0001”

    The paper prints p at a floor (such as p < .001)

  • ConsistentF(2, 12) = 26.006reported p = .0001 · recomputed p < .001

    “F(2,12) = 26.006, p = .0001”

    The paper prints p at a floor (such as p < .001)

  • ConsistentF(2, 12) = 24.017reported p = .0001 · recomputed p < .001

    “F(2,12) =24.017, p = .0001”

  • ConsistentF(2, 9) = 35.524reported p < .0001 · recomputed p < .001

    “F(2,9) = 35.524, p < .0001”

  • ConsistentF(2, 6) = 19.539reported p = .0024 · recomputed p = .002

    “F(2,6) = 19.539, p = .0024”

  • ConsistentF(2, 9) = 7.552reported p = .0119 · recomputed p = .012

    “F(2,9) = 7.552, p = .0119”

  • ConsistentF(2, 9) = 38.395reported p < .0001 · recomputed p < .001

    “F(2,9) = 38.395, p < .0001”

  • ConsistentF(2, 11) = 41.612reported p = .0001 · recomputed p < .001

    “F(2,11) = 41.612, p = .0001”

    The paper prints p at a floor (such as p < .001)

  • ConsistentF(2, 11) = 7.423reported p = .0091 · recomputed p = .009

    “F(2,11) = 7.423, p = .0091”

  • ConsistentF(2, 9) = 11.173reported p = .0036 · recomputed p = .004

    “F(2,9) = 11.173, p = .0036”

  • ConsistentF(2, 6) = 32.882reported p = .0006 · recomputed p < .001

    “F(2,6) =32.882, p = .0006”

16 of 16

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.

  • miR-132 is described as both decreasing and increasing in HD

    Major

    The results include miR-132 among five miRNAs that significantly diminish with increasing HD grade, but later state that miR-132 is significantly upregulated at later stages.

1 of 1

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Authors
Packer, A. N., Xing, Y., Harper, S. Q., Jones, L., & Davidson, B. L.
Affiliations
  • University of Iowa (US)
  • Cardiff University (GB)
Corresponding author
Davidson, Beverly L.
ORCID
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
2008-12-31
Volume
28
Issue
53
Pages
14341-14346
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.2390-08.2008
PMC
PMC3124002
OpenAlex
W2001003536
Semantic Scholar
8dce8a39398d97423fda523d757cbefbbd3b6468
Cited by
679
References
29
Citations by year
2026: 9 · 2025: 15 · 2024: 19 · 2023: 35 · 2022: 20 · 2021: 35 · 2020: 30 · 2019: 25 · 2018: 26 · 2017: 38 · 2016: 43 · 2015: 50 · 2014: 68 · 2013: 66 · 2012: 69
FWCI
16.34
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
Funders
  • Hereditary Disease Foundation
  • National Institutes of Health
  • National Institute on Drug Abuse (R21DA025132)
  • National Institute of Neurological Disorders and Stroke (P01NS050210)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD044093)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
miR-9, rest, CoREST, Huntington's disease, polyglutamine expansion, huntingtin, microRNA regulation, negative feedback loop, neuronal gene expression
MeSH terms
RE1-Silencing Transcription Factor, Aged, Brain, Cell Line, Transformed, DNA-Binding Proteins, Dose-Response Relationship, Drug, Female, Humans, Huntington Disease, Male, Middle Aged, Nerve Tissue Proteins, Postmortem Changes, Repressor Proteins, Transfection, Down-Regulation, Disease Progression, 3' Untranslated Regions, MicroRNAs, Co-Repressor Proteins

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