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Cited by 67MicroRNA in disease regulationPlant Molecular Biology ResearchNeurogenesis and neuroplasticity mechanisms

Expression of miR-15/107 Family MicroRNAs in Human Tissues and Cultured Rat Brain Cells

Open access
Wang, Wang-Xia, Danaher, Robert J., Miller, Craig S., Berger, Joseph R., Nubia, Vega G., Wilfred, Bernard S., Neltner, Janna H., Norris, Christopher M. +1 more·2014·Genomics, Proteomics & Bioinformatics
DOI 10.1016/j.gpb.2013.10.003PMC PMC3975925
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Abstract

The miR-15/107 family comprises a group of 10 paralogous microRNAs (miRNAs), sharing a 5′ AGCAGC sequence. These miRNAs have overlapping targets. In order to characterize the expression of miR-15/107 family miRNAs, we employed customized TaqMan Low-Density micro-fluid PCR-array to investigate the expression of miR-15/107 family members, and other selected miRNAs, in 11 human tissues obtained at autopsy including the cerebral cortex, frontal cortex, primary visual cortex, thalamus, heart, lung, liver, kidney, spleen, stomach and skeletal muscle. miR-103, miR-195 and miR-497 were expressed at similar levels across various tissues, whereas miR-107 is enriched in brain samples. We also examined the expression patterns of evolutionarily conserved miR-15/107 miRNAs in three distinct primary rat brain cell preparations (enriched for cortical neurons, astrocytes and microglia, respectively). In primary cultures of rat brain cells, several members of the miR-15/107 family are enriched in neurons compared to other cell types in the central nervous system (CNS). In addition to mature miRNAs, we also examined the expression of precursors (pri-miRNAs). Our data suggested a generally poor correlation between the expression of mature miRNAs and their precursors. In summary, we provide a detailed study of the tissue and cell type-specific expression profile of this highly expressed and phylogenetically conserved family of miRNA genes.

AI snapshot

Written from the paper’s full text.

TL;DR

The miR-15/107 family shows broad but overlapping expression across human tissues, with miR-107 enriched in brain and several family members enriched in rat neurons versus glia. Mature miRNA levels generally correlate poorly with their precursors, except for brain-specific miR-124.

Key findings

  • In human brain RNA deep-sequencing data, the miR-15/107 family accounted for 1.5–2.0% of total miRNA reads in temporal neocortex gray matter of non-demented controls; miR-16, miR-103, miR-107, and miR-497 were the most highly expressed family members in these brain samples.
  • In H4 glioneuronal cells, miR-16, miR-103, miR-107, and miR-497 shared high target overlap, with 20% of mRNA targets shared by all four miRNAs.
  • miR-107 was enriched in brain tissues (3.25-fold, P < 0.0001), while in primary rat brain cell cultures miR-103, miR-107, miR-195, and miR-497 were neuron-enriched (>2-fold each, P < 0.05).
  • Mature miRNA and precursor expression correlated poorly overall; miR-124 showed the strongest correlation (R² = 0.9189), and miR-103a-2 precursor was higher than miR-103a-1 across tissues (fold increase 1.8–72.8).

Methods

  • Custom TaqMan Low-Density Array RT-qPCR panels profiled mature miRNAs and precursors, including 10 miR-15/107 members and selected other miRNAs, in 11 human autopsy tissues from three individuals (Case2, Case5, Case7).
  • Primary rat cortical neuron, astrocyte, and microglia cultures were generated from Sprague–Dawley rat pups at embryonic day 18; cell-type enrichment was verified by Western blot.
  • miR-15/107 target identification used H4 cells transfected with miRNA duplexes, Affymetrix 1.0 ST Gene microarrays profiling 21,898 annotated genes, N = 3 biological replicates, P < 0.01; expression analyses used Ct values, global mean normalization, unpaired Student t-tests, and Benjamini–Hochberg FDR correction with P < 0.05.

Limitations

  • The paper states that autopsy-derived human tissue introduces potential biases from agonal events, comorbidities, ascertainment/recruitment bias, and RNA degradation; it also notes that miRNA profiling results can vary dramatically across platforms.
  • The paper states that it cannot assess developmental stages, where miR-15/107 family expression is known to change, and that normalization in miRNA studies is challenging; internal controls were too variable to use for normalization (U6 and RNU66 SDs 2.1 and 2.5 Ct; beta-actin and GAPDH SDs 3.4 and 4.0 Ct).
  • Evident from the text: human data come from only three autopsied individuals, the heart tissue of Case5 was unavailable, and the rat primary cultures are cell-type enriched rather than pure preparations.

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

Integrity signals

Registry

Crossref · 10.1016/j.gpb.2013.10.003

Cites

52 of 52 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 45 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    miR-103, miR-195 and miR-497 are expressed at similar levels across various human tissues.

    “miR-103, miR-195 and miR-497 were expressed at similar levels across various tissues”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The 11 human autopsy tissues used have RNA quality sufficient to yield valid miRNA expression profiles.
    • Rests on an assumption: The human tissue samples obtained from three autopsied individuals are representative of normal human tissue expression.
  • Findingown data

    In primary cultures of rat brain cells, miR-103, miR-107, miR-195 and miR-497 are enriched in neurons compared to astrocytes and microglia (>2-fold, P < 0.05).

    “In primary cultures of rat brain cells, several members of the miR-15/107 family are enriched in neurons compared to other cell types in the central nervous system (CNS).”
    • Also stated in: § Members of the miR-15/107 family are enriched in neurons · plain
      “Specifically, 4 members of the miR-15/107 family (miR-103, miR-107, miR-195 and miR-497) were among the neuron-enriched miRNAs (>2-fold enriched for each, P < 0.05).”
    Quote in the paperSubstantial claim
  • Findingown data

    miR-646 is enriched in human kidney.

    “miR-646 was enriched in the kidney.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The 11 human autopsy tissues used have RNA quality sufficient to yield valid miRNA expression profiles.
    • Rests on an assumption: The human tissue samples obtained from three autopsied individuals are representative of normal human tissue expression.
  • Findingown data

    miR-103a-2 precursor is expressed at relatively high levels across all tested human tissues.

    “which was expressed at relatively high levels across all tested tissues.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The 11 human autopsy tissues used have RNA quality sufficient to yield valid miRNA expression profiles.
    • Rests on an assumption: The human tissue samples obtained from three autopsied individuals are representative of normal human tissue expression.
  • Findingown data

    miR-16, miR-15a, miR-15b, miR-424, miR-497, miR-503, miR-646 and other non-miR-15/107 miRNAs tend to show higher expression in non-brain human tissues.

    “whereas miR-16, miR-15a, miR-15b, miR-424, miR-497, miR-503, miR-646 and other non-miR-15/107 miRNAs (miR-20a, miR-23a, miR-27a, miR-27b, miR-30d, miR-143) tended to show higher expression in non-brain tissues”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The 11 human autopsy tissues used have RNA quality sufficient to yield valid miRNA expression profiles.
    • Rests on an assumption: The human tissue samples obtained from three autopsied individuals are representative of normal human tissue expression.
  • May combine two claims. 19
  • Classified as probably not a substantial claim. 17

  • May combine two claims.

    Findingown data

    The miR-124 precursor is exclusively identified in human brain tissues, correlating with its neuronal expression characteristics.

    “The expression of miR-124 precursor was exclusively identified in the brain tissues, which is well correlated with its neuronal expression characteristics.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The 11 human autopsy tissues used have RNA quality sufficient to yield valid miRNA expression profiles.
    • Rests on an assumption: The human tissue samples obtained from three autopsied individuals are representative of normal human tissue expression.

  • May combine two claims.

    Findingown data

    In contrast to much higher levels of mature miR-29a and miR-29c, expression of miR-29a precursor was not detected (Ct > 40) in kidney, liver and spleen; expression of miR-29c was not detected in lung and spleen.

    “In contrast to much higher levels of mature miR-29a and miR-29c, expression of miR-29a precursor was not detected (Ct > 40) in the kidney, liver and spleen; likewise, expression of miR-29c was not detected in lung and spleen.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The 11 human autopsy tissues used have RNA quality sufficient to yield valid miRNA expression profiles.
    • Rests on an assumption: The human tissue samples obtained from three autopsied individuals are representative of normal human tissue expression.

  • May combine two claims.

    Findingown data

    In mature miRNA panels, the standard deviations for U6 and RNU66 are 2.1 and 2.5 Ct, respectively (equivalent to 4.3- and 5.7-fold difference); in the miRNA precursor panel, the standard deviations for beta-actin and GAPDH are 3.4 and 4.0 Ct, respectively (equivalent to 10.6- and 16-fold difference).

    “In mature miRNA panels, the standard deviations for U6 and RNU66 are 2.1 and 2.5 Ct, respectively (equivalent to 4.3- and 5.7-fold difference); and in the miRNA precursor panel, the standard deviations for beta-actin and GAPDH are 3.4 and 4.0 Ct, respectively (equivalent to 10.6- and 16-fold difference).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Endogenous genes are expressed differently across various tissues, making them inappropriate as internal controls.

    “We found that endogenous genes are expressed differently across various tissues, making them inappropriate as internal controls”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The more recently evolved miRNAs (miR-424 and primate-specific miR-646) show relatively low expression, but the mammal-specific miR-195/miR-497 have moderate expression levels.

    “The more recently evolved miRNAs (miR-424 and the primate-specific miR-646) show relatively low expression but the mammal-specific miR-195/miR-497 (physically close to each other on Chromosome 17) have moderate expression levels.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The 11 human autopsy tissues used have RNA quality sufficient to yield valid miRNA expression profiles.
    • Rests on an assumption: The human tissue samples obtained from three autopsied individuals are representative of normal human tissue expression.

  • May combine two claims.

    Findingown data

    miR-124a is strongly expressed in human brain tissues and at lower levels in kidney, spleen and skeletal muscle.

    “miR-124a, a known brain-enriched miRNA, was strongly expressed in brain tissues as expected with lower levels of expression in the kidney, spleen and skeleton muscle samples”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The 11 human autopsy tissues used have RNA quality sufficient to yield valid miRNA expression profiles.
    • Rests on an assumption: The human tissue samples obtained from three autopsied individuals are representative of normal human tissue expression.

  • May combine two claims.

    Premisecitation

    The miR-15/107 family comprises 10 paralogous microRNAs that share a 5′ AGCAGC sequence.

    “The miR-15/107 family comprises a group of 10 paralogous microRNAs (miRNAs), sharing a 5′ AGCAGC sequence.”
    • Also stated in: § Introduction · plain
      “This group of miRNAs shares a sequence (AGCAGC) near the 5′ end [7]”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [7] Finnerty, 2010, The miR-15/107 group of microRNA genes: evolutionary biology, cellular functions, and roles in human diseases, J Mol Biol source
    • cites [8] Zhu, 2012, miR-497 modulates multidrug resistance of human cancer cell lines by targeting BCL2, Med Oncol source
    • cites [9] Moncini, 2011, The role of miR-103 and miR-107 in regulation of CDK5R1 expression and in cellular migration, PLoS One source

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

    Premisecitation

    A subset of miR-15/107 miRNA genes has been detected in mammalian tissues including heart, skeletal muscle, brain, lung, liver, kidney, spleen and placenta.

    “A subset of these miRNA genes has been detected in mammalian tissues including heart, skeletal muscle, brain, lung, liver, kidney, spleen and placenta [25–31].”
    Quote in the paperNot a substantial claim0 of 7 sources checked
    • cites [25] Bargaje, 2010, Consensus miRNA expression profiles derived from interplatform normalization of microarray data, RNA source
    • cites [26] Shingara, 2005, An optimized isolation and labeling platform for accurate microRNA expression profiling, RNA source
    • cites [27] Baskerville, 2005, Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes, RNA source
    • cites [28] Sempere, 2004, Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation, Genome Biol source

      Queued — the background check reaches it, usually within a day.

    • cites [29] Babak, 2004, Probing microRNAs with microarrays: tissue specificity and functional inference, RNA source
    • cites [30] Liu, 2008, Expression profiling of microRNA using oligo DNA arrays, Methods source
    • cites [31] Peltier, 2008, Normalization of microRNA expression levels in quantitative RT-PCR assays: identification of suitable reference RNA targets in normal and cancerous human solid tissues, RNA source

  • May combine two claims.

    Interpretationown data

    miR-103a-2 appears much more highly expressed than miR-103a-1 in all human tissues, suggesting that this gene is the more transcriptionally active source of mature human miR-103.

    “We also note that miR-103a-2 appears much more highly expressed than miR-103a-1 in all human tissues, suggesting that this gene is the more transcriptionally active source of mature human miR-103.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Discordant correlations of miRNA and precursor were also reported for other miRNAs.

    “The discordant correlations of miRNA and the precursor were also reported for other miRNAs [39].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [39] Lee, 2008, Systematic evaluation of microRNA processing patterns in tissues, cell lines, and tumors, RNA source

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    In a paralogous miRNA family, the cumulative impact of those miRNAs must be addressed rather than only focusing on one single gene family member.

    “One key point that is strongly underscored by our data is that in a paralogous miRNA family, the cumulative impact of those miRNAs must be addressed rather than only focusing on one single gene family member.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Individual members of the miR-15/107 group are expressed at medium-to-high levels across many human tissue types but show some tissue- and cell type-specific tropism.

    “Individual members of the miR-15/107 group are expressed at medium-to-high levels across many tissue types but there is some tropism in terms of both tissue- and cell type-specific expression.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The 11 human autopsy tissues used have RNA quality sufficient to yield valid miRNA expression profiles.
    • Rests on an assumption: The human tissue samples obtained from three autopsied individuals are representative of normal human tissue expression.

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

    Study design and conductcitation

    TaqMan assays developed for miRNA detection and validation proved to be sensitive and easy to use.

    “TaqMan assays developed for miRNA detection and validation proved to be sensitive and easy to use [42].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] Schmittgen, 2008, Real-time PCR quantification of precursor and mature microRNA, Methods source

  • May combine two claims.

    Interpretationown data

    We found evidence to support miR-107 expression tropism for the human brain, and also rat neurons versus other cell types.

    “We found evidence to support miR-107 expression tropism for the human brain, and also rat neurons versus other cell types.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductreasoning

    Much of the data derive from human subjects who came to autopsy, which introduces potential biases such as agonal events, comorbidities and ascertainment/recruitment bias, and RNA from autopsy specimens can be degraded.

    “Much of the data derive from human subjects who came to autopsy. This experimental approach introduces potential biases such as those related to agonal events, comorbidities and ascertainment/recruitment bias. RNA from autopsy specimens can also be degraded.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    miR-29a and miR-29b-1, like miR-29b-2 and miR-29c, are apparently co-transcribed as polycistronic primary transcripts.

    “This is interesting because miR-29a and miR-29b-1, like miR-29b-2 and miR-29c, are apparently co-transcribed as polycistronic primary transcripts [15].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Mott, 2010, Transcriptional suppression of mir-29b-1/mir-29a promoter by c-Myc, hedgehog, and NF-kappaB, J Cell Biochem source

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

    Premisecitation

    The human miR-29 family includes three mature members, miR-29a, miR-29b and miR-29c, encoded by two gene clusters.

    “The human miR-29 family includes three mature members, miR-29a, miR-29b and miR-29c, that are encoded by two gene clusters.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Kriegel, 2012, The miR-29 family: genomics, cell biology, and relevance to renal and cardiovascular injury, Physiol Genomics source

  • Classified as probably not a substantial claim.

    Premisecitation

    There is a persistent challenge of normalization in miRNA expression studies across cell types and tissues.

    “There is a persistent challenge of normalization in miRNA expression studies across cell types and tissues [43–47].”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [43] Wylie, 2011, A novel mean-centering method for normalizing microRNA expression from high-throughput RT-qPCR data, BMC Res Notes source
    • cites [44] Lin, 2013, Evaluation of suitable reference genes for normalization of microRNA expression by real-time reverse transcription PCR analysis during longan somatic embryogenesis, Plant Physiol Biochem source
    • cites [45] Lim, 2011, SnoU6 and 5S RNAs are not reliable miRNA reference genes in neuronal differentiation, Neuroscience source
    • cites [46] Brattelid, 2011, Normalization strategy is critical for the outcome of miRNA expression analyses in the rat heart, Physiol Genomics source
    • cites [47] Nelson, 2008, Technical variables in high-throughput miRNA expression profiling: much work remains to be done, Biochim Biophys Acta source

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

    Premisecitation

    In a study of embryos from different species using miRNA in situ hybridization, miR-107 is essentially brain-specific in Japanese killifish, highly expressed in almost all tissues in chicken, but neither pattern is observed in mouse.

    “The complexity of this situation is illustrated in a study of embryos from different species using miRNA in situ hybridization, finding that miR-107 is essentially brain-specific in the Japanese killifish, highly expressed in almost all tissues in chicken, but neither pattern is observed in mouse [38].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Ason, 2006, Differences in vertebrate microRNA expression, Proc Natl Acad Sci U S A source

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

    Study design and conductnone given

    Level of miRNA expression was evaluated using unpaired Student t-test and multiple testing using Benjamin-Hochberg false discovery rate (FDR) method was applied to correct the reported P values.

    “Level of miRNA expression was evaluated using unpaired Student t-test and multiple testing using Benjamin-Hochberg false discovery rate (FDR) method was applied to correct the reported P values.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    The basic observation of poor correlation between levels of mature miRNAs and their precursors had been made previously by others in the context of miR-103 and miR-107 precursors in mice tissues.

    “This basic observation had been made previously by others in the context of miR-103 and miR-107 precursors [37] in mice tissues.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [37] Polster, 2010, Discordant expression of miR-103/7 and pantothenate kinase host genes in mouse, Mol Genet Metab source

  • May combine two claims.

    Study design and conductown data

    The custom array card included internal controls (U6 and RNU66 for mature miRNAs; beta-actin and GAPDH for precursors) but these controls could not be relied on to normalize the data because of substantial variability of these genes expressed in tissues and cells.

    “Although the custom array card included internal controls (U6 and RNU66 for mature miRNAs; beta-actin and GAPDH for the precursors) in the panel, we could not rely on these controls to normalize the data because of the substantial variability of these genes expressed in tissues and cells (Tables S3, S4 and S5).”
    Quote in the paperSubstantial claim

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

    Interpretationcitation

    Since miR-15/107 miRNAs have highly overlapping targets and multiple members are transcribed at constitutively high levels, any therapeutic or diagnostic method based on one family member must also take into account the biological activities of other family members.

    “In other words, since miR-15/107 miRNAs have highly overlapping targets [7,16,41], and multiple members of the gene family are transcribed at constitutively high levels, any therapeutic or diagnostic method based on one family member must also take into account the biological activities of other family members.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [7] Finnerty, 2010, The miR-15/107 group of microRNA genes: evolutionary biology, cellular functions, and roles in human diseases, J Mol Biol source
    • cites [16] Wang, 2010, Individual microRNAs (miRNAs) display distinct mRNA targeting “rules”, RNA Biol source
    • cites [41] Linsley, 2007, Transcripts targeted by the microRNA-16 family cooperatively regulate cell cycle progression, Mol Cell Biol source

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

    Premisecitation

    The brain-specific expression of miR-124a has been demonstrated previously.

    “the brain-specific expression of miR-124a [40] has been demonstrated previously [39,40].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [39] Lee, 2008, Systematic evaluation of microRNA processing patterns in tissues, cell lines, and tumors, RNA source
    • cites [40] Lagos-Quintana, 2002, Identification of tissue-specific microRNAs from mouse, Curr Biol source

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationcitation

    Because miR-15/107 miRNAs co-exist alongside highly-expressed miRNAs with overlapping targets, it is necessary to take into account the expression and activities of paralogous miRNAs, rather than just focusing on individual miRNAs in isolation.

    “Since miR-15/107 miRNAs (like many other miRNAs that have co-evolved with paralogs) co-exist alongside highly-expressed miRNAs with overlapping targets [7,16], these data provide support to the idea that it is necessary to take into account the expression and activities of paralogous miRNAs, rather than just focusing on individual miRNAs in isolation.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [7] Finnerty, 2010, The miR-15/107 group of microRNA genes: evolutionary biology, cellular functions, and roles in human diseases, J Mol Biol source
    • cites [16] Wang, 2010, Individual microRNAs (miRNAs) display distinct mRNA targeting “rules”, RNA Biol source

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

    Premisecitation

    miR-15 and miR-16 expression correlates to particular stages in erythropoiesis.

    “For example, miR-15 and miR-16 expression correlates to particular stages in erythropoiesis [22,23].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [22] Bruchova, 2007, Regulated expression of microRNAs in normal and polycythemia vera erythropoiesis, Exp Hematol source
    • cites [23] Choong, 2007, MicroRNA expression profiling during human cord blood-derived CD34 cell erythropoiesis, Exp Hematol source

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

    Premisecitation

    miRNA profiling results obtained using different platforms can vary dramatically for individual miRNAs despite good overall inter-platform correlation.

    “In addition to the pre-analytical potential challenges, researchers from many laboratories have now found that miRNA profiling results obtained using different platforms can vary dramatically for individual miRNAs despite good overall inter-platform correlation [17–21].”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [17] Git, 2010, Systematic comparison of microarray profiling, real-time PCR, and next-generation sequencing technologies for measuring differential microRNA expression, RNA source
    • cites [18] Wang, 2008, Focus on RNA isolation: obtaining RNA for microRNA (miRNA) expression profiling analyses of neural tissue, Biochim Biophys Acta source
    • cites [19] Chen, 2009, Reproducibility of quantitative RT-PCR array in miRNA expression profiling and comparison with microarray analysis, BMC Genomics source
    • cites [20] Ach, 2008, Measuring microRNAs: comparisons of microarray and quantitative PCR measurements, and of different total RNA prep methods, BMC Biotechnol source
    • cites [21] Willenbrock, 2009, Quantitative miRNA expression analysis: comparing microarrays with next-generation sequencing, RNA source

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

    Premisecitation

    The gene encoding precursors of both miR-29b-1 and miR-29a is located on Chromosome 7, whereas the coding gene for both miR-29b-2 and miR-29c is on Chromosome 1.

    “The gene encoding the precursors of both miR-29b-1 and miR-29a is located on Chromosome 7, whereas the coding gene for both miR-29b-2 and miR-29c is on Chromosome 1 [14].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Kriegel, 2012, The miR-29 family: genomics, cell biology, and relevance to renal and cardiovascular injury, Physiol Genomics source

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

    Premisecitation

    Mature miR-103 can potentially be generated from two primary miRNA transcripts encoded from different chromosomes.

    “The mature miR-103 can potentially be generated from two primary miRNA transcripts that are encoded from different chromosomes [13].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Wilfred, 2007, Energizing miRNA research: a review of the role of miRNAs in lipid metabolism, with a prediction that miR-103/107 regulates human metabolic pathways, Mol Genet Metab source

  • May combine two claims.

    Interpretationreasoning

    These observations confirm the importance and regulatory relevance of the processing steps of miRNA biogenesis.

    “These observations confirm the importance and regulatory relevance of the processing steps of miRNA biogenesis.”
    Quote in the paperSubstantial claim
30 of 30

  • The paper relies on this without support.

    The expression profiles of all miR-15/107 family genes have not been thoroughly described in human tissues or in specific CNS cell types.

    “Although there have been prior expression profiling studies of miRNAs in human tissues (see below), the particular expression profiles of all miR-15/107 family genes have not been thoroughly described either in human tissues or in terms of the specific cell types of the central nervous system (CNS).”

  • The paper relies on this without support.

    The 11 human autopsy tissues used have RNA quality sufficient to yield valid miRNA expression profiles.

    “Eleven human tissues from three autopsied individuals, coded as Case2, Case5 and Case7, with relatively intact RNA, were used in this work.”

  • The paper relies on this without support.

    The human tissue samples obtained from three autopsied individuals are representative of normal human tissue expression.

    “Eleven human tissues from three autopsied individuals, coded as Case2, Case5 and Case7, with relatively intact RNA, were used in this work.”
3 of 3

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.

  • The tissue list names thalamus in one place and thymus in another

    Major

    The abstract lists the thalamus among the 11 sampled tissues, while the Methods list the thymus (THY) instead.

  • The stated number of tested miRNAs exceeds the panel capacity

    Minor

    The paper says 23 miRNAs were tested for precursor-mature correlation, but describes panels of 24 assays each with two endogenous controls. That leaves at most 22 miRNA assays per panel.

  • The number of additional miRNAs differs between sections

    Minor

    The Results say the panel included 10 selected miRNAs besides the 10 family members; the Methods say it included 12 other selected miRNAs.

3 of 3

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Authors
Wang, W.-X., Danaher, R. J., Miller, C. S., Berger, J. R., Nubia, V. G., Wilfred, B. S., Neltner, J. H., Norris, C. M., & Nelson, P. T.
Affiliations
  • University of Kentucky (US)
  • Department of Neurology, University of Kentucky , Lexington, KY, 40536 , USA
  • Sanders-Brown Center on Aging, University of Kentucky , Lexington, KY, 40536 , USA
Corresponding author
Nelson, Peter T.
ORCID
Venue
Genomics, Proteomics & Bioinformatics
Publisher
Oxford University Press (OUP)
Published
2014-01-28
Volume
12
Issue
1
Pages
19-30
ISSN
  • 1672-0229 (ISSN-L)
  • 2210-3244
DOI
10.1016/j.gpb.2013.10.003
PMC
PMC3975925
OpenAlex
W2084259236
Semantic Scholar
dde3dc1b11c78fe24b5a075f46f2716b8da95487
Cited by
67
References
52
Citations by year
2026: 2 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 2 · 2021: 6 · 2020: 12 · 2019: 7 · 2018: 4 · 2017: 6 · 2016: 7 · 2015: 10 · 2014: 1
FWCI
2.49
Type
journal article
Language
en
Open access
Licence
Locations
  • Genomics Proteomics & Bioinformatics (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • UKnowledge (University of Kentucky) (submittedVersion, cc-by-nc-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
National Institutes of Health (AG042419, NS085830, AG028 383)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
miRNA expression profiling, tissue-specific gene expression, cell type-specific gene expression, cortical neurons, astrocytes, microglia, pri-miRNA, miR-107, miR-103, miR-195, miR-497, human tissue, central nervous system
MeSH terms
Animals, Brain, Cells, Cultured, Humans, Neurons, Cluster Analysis, Microglia, Gene Expression Profiling, MicroRNAs, Rats

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-11-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-11-06.

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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