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Cited by 82MicroRNA in disease regulationAdipokines, Inflammation, and Metabolic DiseasesMetabolism, Diabetes, and Cancer

MicroRNA 7 Impairs Insulin Signaling and Regulates A β Levels through Posttranscriptional Regulation of the Insulin Receptor Substrate 2, Insulin Receptor, Insulin-Degrading Enzyme, and Liver X Receptor Pathway

Open access
Fernández-de Frutos, Mario, Galán-Chilet, Inmaculada, Goedeke, Leigh, Kim, Byungwook, Pardo-Marqués, Virginia, Pérez-García, Ana, Herrero, J. Ignacio, Fernández-Hernando, Carlos +2 more·2019·Molecular and Cellular Biology
DOI 10.1128/mcb.00170-19PMC PMC6817752
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Abstract

Brain insulin resistance is a key pathological feature contributing to obesity, diabetes, and neurodegenerative disorders, including Alzheimer’s disease (AD). Besides the classic transcriptional mechanism mediated by hormones, posttranscriptional regulation has recently been shown to regulate a number of signaling pathways that could lead to metabolic diseases. Here, we show that microRNA 7 (miR-7), an abundant microRNA in the brain, targets insulin receptor (INSR), insulin receptor substrate 2 (IRS-2), and insulin-degrading enzyme (IDE), key regulators of insulin homeostatic functions in the central nervous system (CNS) and the pathology of AD. In this study, we found that insulin and liver X receptor (LXR) activators promote the expression of the intronic miR-7-1 in vitro and in vivo, along with its host heterogeneous nuclear ribonucleoprotein K (HNRNPK) gene, encoding an RNA binding protein (RBP) that is involved in insulin action at the posttranscriptional level. Our data show that miR-7 expression is altered in the brains of diet-induced obese mice. Moreover, we found that the levels of miR-7 are also elevated in brains of AD patients; this inversely correlates with the expression of its target genes IRS-2 and IDE. Furthermore, overexpression of miR-7 increased the levels of extracellular Aβ in neuronal cells and impaired the clearance of extracellular Aβ by microglial cells. Taken together, these results represent a novel branch of insulin action through the HNRNPK–miR-7 axis and highlight the possible implication of these posttranscriptional regulators in a range of diseases underlying metabolic dysregulation in the brain, from diabetes to Alzheimer’s disease.

AI snapshot

Written from the paper’s full text.

TL;DR

miR-7 is an abundant brain microRNA that directly represses insulin signaling and Alzheimer’s disease–related targets, including INSR, IRS-2, and IDE. Its expression is induced by insulin/LXR via SREBP1c and is elevated in obese mouse brains and AD patient cortex, where it may impair insulin signaling and Aβ clearance.

Key findings

  • miR-7 overexpression in mouse N2a neuronal cells significantly decreased IRS-2, AKT, IGF1R, and IDE mRNA, while miR-7 inhibition increased INSR, IRS-1, IRS-2, AKT, IGF1R, and IDE; luciferase assays confirmed direct repression of INSR, IRS-2, and IDE 3′ UTRs.
  • miR-7 impaired insulin signaling: after 100 nM insulin, miR-7 overexpression markedly reduced p-AKT at all time points and p-GSK3β except at time zero and 30 min.
  • Insulin and LXR activation induced HNRNPK and miR-7-1 in vitro and in vivo; SREBP1c overexpression increased HNRNPK and precursor/mature miR-7, and an LXR diet induced miR-7a-1, mature miR-7, HNRNPK mRNA, and HNRNPK protein in mouse brain.
  • miR-7 was elevated in brains of diet-induced obese mice and high-cholesterol-fed mice, and in AD patient cortex compared with healthy subjects, inversely correlating with IRS-2 and IDE; miR-7 overexpression increased extracellular Aβ in neuronal cells and impaired Aβ clearance by microglial cells.

Methods

  • In vitro studies used mouse N2a neuronal cells, human SHSY5Y cells, BV-2 microglial cells, and COS-7 cells for luciferase reporter assays; cells were transfected with miR-7-5p mimic or inhibitor, treated with 100 nM insulin or 3 µM T0901317, and analyzed by qRT-PCR, Western blotting, Northern blotting, and luciferase assays.
  • Mouse studies used 8-week-old male C57BL/6 mice in high-fat diet, diet-induced obesity, streptozotocin-induced type 1 diabetes, fasting/glucose injection, and LXR-diet models; brain tissues were dissected for gene/protein expression.
  • Human postmortem brain samples from area 9 were obtained from AD patients and healthy subjects; Table 1 lists 6 control and 7 AD cases, and Fig. 10 reports n = 5 per group. Statistical analyses included t tests, one-way ANOVA with Bonferroni correction, Kolmogorov-Smirnov normality testing, and Mann-Whitney tests when nonparametric.

Limitations

  • The paper states that further analyses are necessary to explore potential direct transcriptional activation of HNRNPK/miR-7 by LXR and that additional regulation cannot be excluded.
  • Evident from the text: human brain findings are correlational and based on a small postmortem sample, with a discrepancy between Fig. 10’s stated n = 5 per group and Table 1’s 6 control/7 AD cases.
  • Evident from the text: many mechanistic conclusions derive from cell lines and mouse models, so the causal role of miR-7 in human AD progression remains to be established.

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

Integrity signals

Registry

Crossref · 10.1128/mcb.00170-19

Cites

40 of 40 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 22 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Overexpression of miR-7 impairs the clearance of extracellular amyloid-beta by microglial cells.

    “impairs the clearance of extracellular A␤ by microglial cells (Fig. 10C and D).”
    Quote in the paperSubstantial claim
  • Findingown data

    miR-7 significantly decreased ABCA1 and LXR-beta mRNA levels in N2a cells.

    “miR-7 significantly decreased the levels of ABCA1 and LXR␤ mRNAs in N2a cells (Fig. 9A).”
    Quote in the paperSubstantial claim
  • Findingown data

    Similar effects on insulin signaling pathway genes were found at the protein level after miR-7 modulation in N2a cells.

    “Similar results were found at the protein level when we assessed their expression by Western blotting (Fig. 4C).”
    Quote in the paperSubstantial claim
  • Findingown data

    miR-7 expression is elevated in the brain of mice fed a high-cholesterol diet.

    “Similar results were observed in mice fed a high cholesterol diet (Fig. 10B).”
    Quote in the paperSubstantial claim
  • Findingown data

    miR-7 expression is significantly elevated in the brain of diet-induced obese mice compared to control diet mice.

    “Our results showed that miR-7 expression is significantly elevated in the brain of diet-induced obese (DIO) mice compared to those in mice fed a control diet (Fig. 10A).”
    Quote in the paperSubstantial claim
  • May combine two claims. 21
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 18

  • May combine two claims.

    Findingown data

    miR-7a-1 is abundantly expressed in mouse brain and liver, while precursors of miR-7a-2 and miR-7b are highly expressed in brain compared with other organs.

    “Analysis of precursors by quantitative real-time PCR (qRT-PCR) in mouse tissues shows that miR-7a-1 is abundantly expressed in the brain and in the liver, while precursors of miR-7a-2 and miR-7b are highly expressed in the brain compared with other organs (Fig. 1D).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Bioinformatic target prediction shows that potential miR-7 targets are enriched in insulin signaling and related pathways, including INSR, IRS-1, PI3K, and IGF1R, and in Alzheimer's disease genes, most notably IDE.

    “Using bioinformatic prediction algorithms and gene ontology (GO) enrichment analysis, we found that potential miR-7 targets are enriched in gene clusters involved in insulin signaling and related pathways (INSR, IRS-1, phosphatidylinositol 3-kinase [PI3K], and IGF1R) and AD (most notably IDE).”
    Quote in the paperSubstantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    miR-7 is highly abundant in the brain, with relatively higher expression than in other organs, and is highly abundant in the hypothalamus.

    “Analysis of the mature form indicates that the miR-7 expression level is relatively higher in brain than in other organs (Fig. 1D).”
    • Also stated in: § miR-7 is highly abundant in the brain and targets key elements of the insulin signaling pathway and Alzheimer's disease. · plain
      “Further analysis by Northern blotting of different mouse brain tissues revealed that miR-7 is highly abundant in the hypothalamus (Fig. 1E).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    An LXR diet induces ABCA1 and SREBP1c, miR-7a-1 precursor and mature miR-7, and HNRNPK mRNA and protein in mouse brain.

    “qRT-PCR experiments showed a significant induction of the LXR target genes encoding ABCA1 and SREBP1c in the brains of mice fed an LXR diet compared to a control diet (Fig. 8K).”
    • Also stated in: § miR-7-1 transcription is induced by SREBP1 in vitro and in vivo. · plain
      “More importantly, the miR-7a-1 precursor and mature miR-7 (Fig. 8J), together with HNRNPK mRNA and protein (Fig. 8I and L), were also induced in the brain in response to LXR activation and SREBP1c induction in vivo”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    LXR activation with T0901317 induces HNRNPK mRNA and protein, precursor and mature miR-7, and ABCA1 and SREBP1 in N2a cells.

    “LXR activation led to a significant induction of HNRNPK mRNA (Fig. 8E) and protein (Fig. 8H) and the precursor and mature forms of miR-7 (Fig. 8F) as well as the upregulation of its classic transcriptional targets, including ABCA1 and SREBP1 (Fig. 8G and H).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    miR-7 significantly repressed INSR, IRS-2, and IDE 3'UTR activities, and mutation of the miR-7 target sites relieved this repression.

    “Our data show that miR-7 significantly repressed INSR, IRS-2, and IDE 3=-UTR activities, and the mutation of the miR-7 target sites relieved the repression of the INSR, IRS-2, and IDE 3= UTRs, which is consistent with its direct interaction with the mRNAs studied.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In vivo, glucose injection after starvation induces HNRNPK mRNA and protein and miR-7 levels in mouse hypothalamus.

    “Using this approach, we found that HNRNPK mRNA and protein levels of HNRNPK were induced after 1 h of glucose injection, compared with those in the hypothalamus of starved mice, consistent with its transcriptional regulation in response to insulin in the brain (Fig. 6D).”
    • Also stated in: § miR-7-1 is synchronously induced with its host HNRNPK gene upon insulin stimulation and in vitro and in vivo. · plain
      “Our Northern blot analysis showed that miR-7 levels are also upregulated in the hypothalamus under the same conditions (Fig. 6E).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Insulin increases HNRNPK mRNA and protein levels and the precursor and mature forms of miR-7a-1 in N2a cells.

    “Our results showed that insulin increased HNRNPK mRNA and protein levels (Fig. 6A), and this induction correlated with significant increases in the precursor and mature forms of miR-7a-1 (Fig. 6B and C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Overexpression of nuclear SREBP1c significantly increased HNRNPK expression, precursor and mature miR-7, and SREBP1 and FASN in N2a cells.

    “The overexpression of nSREBP1c significantly increased the expression of HNRNPK (Fig. 8A), the precursor and mature forms of miR-7 (Fig. 8B), as well as SREBP1 and its target gene encoding fatty acid synthase (FASN) (Fig. 8C and D).”
    Quote in the paperSubstantial claim

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

    Findingown data

    Human and mouse HNRNPK promoters contain predicted Sp1, E-box, and NFY binding sites.

    “Sequence alignment of the human and mouse HNRNPK promoters (minus strand) showing the localization of predicted Sp1 (orange, 85% confidence; purple, 90% confidence), E-box (green), and NFY (blue) binding sites found using Consite (http://consite.genereg.net/cgi-bin/consite)and Genomatix (http://www .genomatix.de).”
    Quote in the paperNot a substantial claim

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

    Findingnone given

    Human miR-7-1 and murine miR-7a-1 are located in introns 16 and 17 of the HNRNPK gene, respectively.

    “Human miR-7-1 and murine miR-7a-1 are located in introns 16 and 17 of the HNRNPK gene, respectively.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    IRS-2 and IDE are significantly decreased in cortex from human AD patients compared with healthy subjects.

    “qRT-PCR analysis of IRS-2 and IDE in cortex from human AD patients and matching healthy human subjects (n ϭ 5 per group).*, P Ͻ 0.05 compared with control healthy subjects.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Postmortem human brain samples from AD patients are representative of AD pathology.

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

    Findingnone given

    miR-7-2 and miR-7-3 are located in intergenic regions of human chromosomes 15 and 19.

    “miR-7-2 and miR-7-3 are located in intergenic regions of human chromosomes 15 and 19.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Intranasal administration of insulin improves cognitive decline in Alzheimer's disease patients.

    “Furthermore, intranasal administration of insulin has been shown to improve cognitive decline in AD patients (3).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3]

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

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

    Premisecitation

    ABCA1 affects the lipidation status of ApoE in the brain, which may facilitate proteolytic degradation of amyloid-beta.

    “ABCA1, one of the most studied transcriptional targets of LXR, affects the lipidation status of ApoE in the brain, which in turn may facilitate the proteolytic degradation of A␤ (30).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30]

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

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    MicroRNAs repress translation or induce mRNA degradation by binding to the 3' untranslated regions of target mRNAs.

    “By binding to the 3= untranslated regions (UTRs) of target mRNAs, miRNAs repress translation or induce mRNA degradation (4,5).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [4]

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

    • cites [5]

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

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

    Premisecitation

    Individuals with diabetes have a 1.5- to 2.0-fold higher risk of developing Alzheimer's disease than individuals without diabetes.

    “Individuals with diabetes have a 1.5-to 2.0-fold-higher risk of developing AD than individuals without diabetes (1).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1]

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

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

    Premisecitation

    miR-7 is an evolutionarily highly conserved microRNA considered a prototypical neuroendocrine microRNA, highly expressed in neuroendocrine organs such as pancreas and brain.

    “miR-7 is an evolutionarily highly conserved miRNA that is considered a prototypical neuroendocrine miRNA, being highly expressed in neuroendocrine organs such as the pancreas and brain (12).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12]

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

  • May combine two claims.

    Premisecitation

    Insulin can exert neuroprotective effects by preventing Tau hyperphosphorylation and promoting extracellular degradation of amyloid-beta through regulation of insulin-degrading enzyme, a key molecular link between Alzheimer's disease and diabetes.

    “Insulin can exert neuroprotective effects by preventing Tau hyperphosphorylation and promoting the extracellular degradation of A␤ through the regulation of insulin-degrading enzyme (IDE), which represents a key molecular link between AD and diabetes (2).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [2]

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

  • May combine two claims.

    Premisecitation

    IDE expression influences amyloid-beta levels in vitro and in vivo.

    “IDE expression, which has been shown to influence A␤ levels in vitro and in vivo (33)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [33]

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

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

    Premisecitation

    HNRNPK is an RNA binding protein recently shown to be involved in insulin actions at the posttranscriptional level.

    “miR-7-1 is an intronic miRNA located in HNRNPK, an RBP that was recently shown to be involved in insulin actions at the posttranscriptional level (16).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16]

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

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

    Study design and conductcitation

    N2a cells are a fast-growing mouse neuroblastoma cell line widely used to study neurotoxicity, metabolism, microRNAs, and Alzheimer's disease.

    “N2a cells are a fast-growing neuroblastoma cell line from mouse that has been widely used to study neurotoxicity, metabolism, miRNAs, and Alzheimer's disease (11).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11]

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

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

    Premisecitation

    miR-7 expression is highly regulated in the brain by other posttranscriptional regulators such as RNA binding proteins and miRNA sponges.

    “Nevertheless, miR-7 expression seems to be highly regulated in the brain by several other posttranscriptional regulators, such as RNA binding proteins (RBPs) (14) and miRNA sponges (15), suggesting its important role in the CNS.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [14]

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

    • cites [15]

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

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    Overproduction of miR-7 during metabolic dysregulation could ameliorate the neuroprotective actions of insulin and LXR in the brain, promoting later insulin resistance and amyloidosis, thus representing a molecular link between insulin resistance and Alzheimer's disease at the posttranscriptional level.

    “In the context of our study, it is conceivable that overproduction of miR-7 during states of metabolic dysregulation, as in hyperinsulinized brains during obesity, metabolic syndrome, and T2DM (34), could ameliorate the neuroprotective actions of insulin and LXR in the brain, promoting later IR and amyloidosis, thus representing a molecular link between insulin resistance and AD at the posttransc”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [34]

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

    • Rests on an assumption: SREBP1c is the predominant isoform of SREBP1 upregulated in response to insulin.

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

    Study design and conductnone given

    All constructs were confirmed by sequencing.

    “All constructs were confirmed by sequencing.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Verification of miR-7 overexpression and knockdown was performed using quantitative PCR (qPCR).

    “Verification of miR-7 overexpression and knockdown was performed using quantitative PCR (qPCR) as described below.”
    Quote in the paperSubstantial claim

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

    Premiseown data

    The active promoter of the HNRNPK region correlates with CpG islands and enriched H3K4Me3 histone marks.

    “The active promoter of the HNRNPK region correlates with CpG islands (green) and enriched H3K4Me3 histone marks.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    All experiments were performed in triplicate and repeated independently twice.

    “All experiments were performed in triplicate and repeated independently twice.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Experiments were performed in triplicate at least three times.

    “Experiments were performed in triplicate at least three times.”
    Quote in the paperNot a substantial claim

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

    Premiseown data

    ChIP-assayed transcription factors at the HNRNPK promoter include SP1, SREBP1, and SREBP2.

    “ChIP-assayed transcription factors shown include SP1, SREBP1, and SREBP2 (highlighted in red).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    miR-7 acts as a dual negative regulator of insulin and LXR actions in the brain and potentially of amyloid-beta metabolism during Alzheimer's disease progression.

    “These data, together with our above-described in vitro results, support the hypothesis that miR-7 acts as a dual negative regulator of insulin and LXR actions in the brain and, potentially, A␤ metabolism during the progression of AD.”
    Quote in the paperSubstantial claim
31 of 31

  • The paper relies on this without support.

    SREBP1c is the predominant isoform of SREBP1 upregulated in response to insulin.

    “As it has been reported that SREBP1c is the predominant isoform of SREBP1 upregulated in response to insulin, we hypothesized that it probably acts as a transcriptional regulator of HNRNPK and miR-7-1 expression.”

  • The paper relies on this without support.

    MicroRNAs with biological significance usually target entire pathways rather than a single mRNA involved in a biological function.

    “In this regard, it is generally accepted that miRNAs with biological significance usually target entire pathways rather than a single mRNA involved in a biological function.”

  • The paper relies on this without support.

    The DIO/HFD/STZ mouse models recapitulate human obesity/diabetes relevant to the study.

    “For DIO studies, 8-week-old male wild-type (WT) mice (n ϭ 5 per group) were fed a chow diet or a 60% fat diet (catalog number D12492; Research Diets) for 10 weeks.”

  • The paper relies on this without support.

    Postmortem human brain samples from AD patients are representative of AD pathology.

    “Postmortem human brains (area 9) without any severe neurological and psychological disorders and brains with severe dementia of the Alzheimer type were obtained from autopsies performed at the University of Kentucky (Peter T. Nelson).”

  • The paper relies on this without support.

    Transfection of miR-7 mimic recapitulates endogenous miR-7 function.

    “Cells (ϳ70% confluence) were transfected with 40 nM the miRIDIAN miRNA mimic (miR-7-5p) or with 60 nM the miRIDIAN miRNA inhibitor (Inh-miR-7-5p) (Dharmacon) by utilizing Lipofectamine RNAiMax (Invitrogen) and studied 48 h later.”
5 of 5

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.

  • Figure 1 Northern blot is cited as panel E but caption labels it D

    Minor

    The Results direct readers to Figure 1E for the Northern blot of mouse brain tissues, while the figure caption identifies that experiment as panel D. The caption describes panel E as a sequence alignment.

  • Glucose injection dose differs tenfold between Methods and Figure 6

    Minor

    The mouse-study methods specify 2 g/kg of glucose, whereas the Figure 6 caption specifies 20 g/kg for the fasting-and-glucose-injection experiment. The reported dose is therefore inconsistent.

2 of 2

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Authors
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.
Affiliations
  • IMDEA Research Institute of Food and Health Sciences
  • Genomic and Genetic Diagnosis Unit, Biomedical Research Institute Hospital Clinic of Valencia (INCLIVA)
  • Yale University (US)
  • Stark Neurosciences Research Institute, Indiana University School of Medicine
  • Madrid Institute for Advanced Studies (ES)
  • Consejo Superior de Investigaciones Científicas (ES)
  • Vascular Biology and Therapeutics Program, Yale University School of Medicine
  • Indiana University Indianapolis (US)
Corresponding author
Ramírez, Cristina M.
ORCID
Venue
Molecular and Cellular Biology
Publisher
Informa UK Limited
Published
2019-11-01
Volume
39
Issue
22
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
DOI
10.1128/mcb.00170-19
PMC
PMC6817752
OpenAlex
W2971463262
Semantic Scholar
53fc585a32da6f093221eaae640685e1ffee9368
Cited by
82
References
40
Citations by year
2026: 8 · 2025: 11 · 2024: 13 · 2023: 12 · 2022: 15 · 2021: 13 · 2020: 10
FWCI
2.63
Type
journal article
Language
en
Open access
Licence
doi.org/10.1080/policies-text-data-mining (tdm)
Locations
  • Molecular and Cellular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion)
  • PMC
Funders
  • National Institutes of Health (R01AG054102, R01AG053500, R01AG053242, R21AG050804)
  • HHS | National Institutes of Health (R35HL135820)
  • American Heart Association (SDG23000025)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
microRNA-7, insulin signaling, insulin resistance, Alzheimer's disease, amyloid-beta, post-transcriptional regulation, insulin receptor substrate 2, insulin receptor, insulin-degrading enzyme, liver X receptor, hnRNP K, microRNA host gene, diet-induced obesity
MeSH terms
Liver X Receptors, Animals, Brain, Humans, Insulin, Insulin Resistance, Insulysin, Neurons, Receptor, Insulin, RNA Processing, Post-Transcriptional, Signal Transduction, Amyloid beta-Peptides, Heterogeneous-Nuclear Ribonucleoprotein K, MicroRNAs, Cell Line, Tumor, Mice, Insulin Receptor Substrate Proteins

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