Cited by 968MicroRNA in disease regulationGene expression and cancer classificationPlant Molecular Biology Research

The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index; 14 of the 34 sources its claims cite were checked for support.

Distribution of miRNA expression across human tissues

Open access

Abstract

We present a human miRNA tissue atlas by determining the abundance of 1997 miRNAs in 61 tissue biopsies of different organs from two individuals collected post-mortem. One thousand three hundred sixty-four miRNAs were discovered in at least one tissue, 143 were present in each tissue. To define the distribution of miRNAs, we utilized a tissue specificity index (TSI). The majority of miRNAs (82.9%) fell in a middle TSI range i.e. were neither specific for single tissues (TSI > 0.85) nor housekeeping miRNAs (TSI < 0.5). Nonetheless, we observed many different miRNAs and miRNA families that were predominantly expressed in certain tissues. Clustering of miRNA abundances revealed that tissues like several areas of the brain clustered together. Considering -3p and -5p mature forms we observed miR-150 with different tissue specificity. Analysis of additional lung and prostate biopsies indicated that inter-organism variability was significantly lower than inter-organ variability. Tissue-specific differences between the miRNA patterns appeared not to be significantly altered by storage as shown for heart and lung tissue. MiRNAs TSI values of human tissues were significantly (P = 10(-8)) correlated with those of rats; miRNAs that were highly abundant in certain human tissues were likewise abundant in according rat tissues. We implemented a web-based repository enabling scientists to access and browse the data (https://ccb-web.cs.uni-saarland.de/tissueatlas).

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This paper presents a human miRNA tissue atlas by profiling 1,997 mature miRNAs across 61 post-mortem tissue biopsies from two male individuals, with 1,364 miRNAs detected in at least one tissue and 143 detected in all tissues. It reports tissue-specific miRNA patterns, a web repository, and conserved tissue specificity between human and rat.

Key findings

  • Of 1,997 mature miRNAs, 633 (31.7%) were not detected in any tested tissue; 1,364 were detected in at least one tissue, and 143 (10.5%) were found in all tissues.
  • Most detected miRNAs had intermediate tissue specificity: 82.9% fell in a middle TSI range, neither tissue-specific (TSI > 0.85) nor housekeeping (TSI < 0.5); in quantile-normalized data, 83.7% of miRNAs in the first body and 88.8% in the second body had intermediate TSI values.
  • Tissue-specific examples included miR-1–3p as the overall most tissue-specific miRNA, high in muscle and myocardium; miR-122–5p in liver, miR-7–5p in pituitary gland, miR-205–5p in skin, and miR-507/miR-514a-3p/miR-509–5p in testis.
  • Human and rat tissue specificity was significantly correlated (TSI correlation 0.362, P = 9 × 10−8; permutation average correlation 0), and inter-individual variability was significantly lower than inter-organ variability in lung and prostate analyses (P < 10−16).

Methods

  • Profiled 61 tissue biopsies from two male cadavers (65-year-old with multiple myeloma; 59-year-old with no signs of cancer) using Agilent SurePrint 8 × 60K Human V19 miRNA microarrays, covering 1,997 human miRNAs present in both miRBase V19 and V21.
  • Pre-analytics included 44 tissue miRNomes for reproducibility and storage/degradation analyses, 16 additional normal lung biopsies from different individuals, and GEO datasets from normal gastric and prostate tissues.
  • Calculated a tissue specificity index (TSI) for each miRNA, performed hierarchical clustering, miRNA family and co-expression analyses, and compared human TSI values with rat data from GEO series GSE52754; analyses used raw, quantile-normalized, and variance-stabilized normalized data.

Limitations

  • The paper states that autopsy samples from only two male individuals provide only a snapshot of full miRNA expression variability, and that age, sex, and disease status can influence miRNA patterns.
  • The authors state they cannot exclude that some tissue-specific miRNAs might be affected by sample degradation, although storage between 1 and 14 days at 4°C had limited overall impact on tissue miRNA patterns.
  • The paper notes that microarray analysis cannot detect presently unknown miRNAs or miRNA isoforms, and that normalization choice can substantially influence results; these are stated limitations of the platform and analysis approach.

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

Integrity signals

Registry

Crossref · 10.1093/nar/gkw116

Cites

29 of 29 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

14 of 34 cited sources checked · 7 supported · 0 flagged · accuracy not yet measured

Show all 73 claims

  • Probably not a substantial claim. 19
  • It may state two separate claims as one. 35
  • The quote only partly states this claim. 4
51 of 51
  • The paper relies on this without support.

    The two post-mortem male individuals are representative of the general human population for tissue miRNA distribution.

    “Tissues analysed in this study originated from two male bodies.”
    “we measured all miRNA profiles from only two different individuals to minimize inter-individual variability.”
  • The paper relies on this without support.

    The first individual's multiple myeloma did not substantially alter the miRNA profiles of his non-tumor tissues.

    “The first body was from a 65-year-old male patient, who suffered from multiple myeloma, a cancer that forms in a type of white blood cells (plasma cells).”
  • The paper relies on this without support.

    RNA integrity values between 1.8 and 2.7 in autopsy samples are sufficient for reliable miRNA profiling.

    “As expected for autopsy samples, the RNA integrity values (RIN) ranged between 1.8 and 2.7.”
  • The paper relies on this without support.

    The majority of studies investigate differential expression in only one organ/tissue.

    “Although there is ample evidence for differential miRNA expression in different human tissues, the majority of studies investigate differential expression in only one organ/tissue.”
  • The paper relies on this without support.

    Results of studies are not easily comparable due to different identification methods and normalization strategies, limiting their value for comparison of miRNA expression in different tissues.

    “Due to the different identification methods and normalization strategies, the results of these studies are not easily comparable limiting their value for comparison of miRNA expression in different tissues.”
  • The paper relies on this without support.

    Biopsies will be mostly taken from patients with affected organs.

    “biopsies will be mostly taken from patients with affected organs”
  • The paper relies on this without support.

    High inter-individual differences can mask tissue-specific differences of miRNA abundances.

    “high inter-individual differences can mask tissue-specific differences of miRNA abundances”
  • The paper relies on this without support.

    A bias is likely introduced by multiple centres involved in tissue collections.

    “a bias is likely introduced by multiple centres that are involved in tissue collections”
  • The paper relies on this without support.

    Samples of vital organs (e.g., thalamus, spinal cord, cerebellum) are not available from biopsies.

    “samples of vital organs, e.g. thalamus, spinal cord or cerebellum, are not available”
  • The paper relies on this without support.

    RNA degradation in autopsy samples due to storage duration, advanced age, or disease status of body donors.

    “with the disadvantage of RNA degradation in the samples due to the storage duration of the body and the advanced age or the disease status of the body donors”
  • The paper relies on this without support.

    Many normalization techniques can have a substantial influence on the results.

    “Many techniques that are frequently applied such as variance stabilizing normalization or quantile normalization can have a substantial influence on the results.”
11 of 11

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?

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-122-5p is called exclusive to liver despite detection elsewhere

    Minor

    The results call miR-122-5p exclusively expressed in liver, whereas the discussion reports its expression in three other tissue types.

  • Human-rat TSI correlation has two stated P-values

    Minor

    The abstract gives P = 10−8, while the results give P = 9 × 10−8 for the human-rat TSI correlation.

  • The 16 additional lung biopsies are described as both normal and cancer tissue

    Minor

    The methods describe these biopsies as normal lung tissue, but the additional-data section calls them lung cancer tissues.

  • Co-expression correlations are identified as both Pearson and Spearman

    Minor

    The methods and Figure 6B identify the co-expression measure as Spearman correlation, but the results say the 0.95 cutoff was applied to Pearson correlation.

4 of 4

Citations

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Metadata

Authors
Ludwig, N., Leidinger, P., Becker, K., Backes, C., Fehlmann, T., Pallasch, C., Rheinheimer, S., Meder, B., Stähler, C., Meese, E., & Keller, A.
Affiliations
  • Saarland University (DE)
  • Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (DE)
  • University Hospital Heidelberg (DE)
  • Siemens Healthineers (Germany) (DE)
Corresponding author
Keller, Andreas
Venue
Nucleic Acids Research
Published
2016-02-25
Volume
44
Issue
8
Pages
3865-3877
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
OpenAlex
W2288482887
Cited by
968
References
29
Citations by year
2026: 45 · 2025: 73 · 2024: 93 · 2023: 97 · 2022: 104 · 2021: 138 · 2020: 141 · 2019: 109 · 2018: 88 · 2017: 61 · 2016: 17
FWCI
32.73
Type
journal article
Language
en
Open access
Locations
  • Nucleic Acids Research (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
Universität des Saarlandes
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
Keywords
microRNA expression, human tissue atlas, miRNA abundance, miR-150, brain, lung, prostate, heart, rat comparison, postmortem tissue, web-based repository
MeSH terms
Adult, Aged, Animals, Humans, Male, Organ Specificity, Tissue Distribution, Reproducibility of Results, Databases, Nucleic Acid, MicroRNAs, Rats

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