Evidence map›Paper›PMID 27576563›Full record

ArticleBMC genomics2016

The Rat microRNA body atlas; Evaluation of the microRNA content of rat organs through deep sequencing and characterization of pancreas enriched miRNAs as biomarkers of pancreatic toxicity in the rat and dog.

Aaron Smith, John Calley, Sachin Mathur, Hui-Rong Qian, Han Wu, Mark Farmen, Florian Caiment, Pierre R Bushel, Jianying Li, Craig Fisher and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC genomics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.

  1. Urinary miRNA Biomarkers of Drug-Induced Kidney Injury and Their Site Specificity Within the Nephron.Toxicological sciences : an official journal of the Society of Toxicology · 2021
    Pooled it
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  17. Overexpression of miR-9 in the Nucleus Accumbens Increases Oxycodone Self-Administration.The international journal of neuropsychopharmacology · 2019
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 2 countries.

Aaron SmithDepartment of Investigative Toxicology, Non Clinical Safety Assessment and Pathology, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, 46285, IN, USA. smithat@lilly.com.
John CalleyDepartment of TTX Bioinformatics, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, 46285, IN, USA.
Sachin MathurDepartment of TTX Bioinformatics, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, 46285, IN, USA.
Hui-Rong QianDepartment of Discovery and Development Statistics, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, 46285, IN, USA.
Han WuDepartment of Discovery and Development Statistics, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, 46285, IN, USA.
Mark FarmenDepartment of Discovery and Development Statistics, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, 46285, IN, USA.
Florian CaimentDepartment of Toxicogenomics, Maastricht University, Universiteitsingel, Maastricht, The Netherlands.
Pierre R BushelNational Institute of Environmental Health Sciences, Biostatistics Branch, Durham, NC, USA.
Jianying LiKelly Government Solutions, Research Triangle Park, Durham, NC, 27709, USA.
Craig FisherDrug Safety Evaluation, Takeda Pharmaceuticals International Company, Deerfield, USA.
Patrick KirbyDrug Safety Evaluation, Takeda Pharmaceuticals International Company, Deerfield, USA.
Erik KoenigMolecular Pathology, Takeda Pharmaceuticals International Company, Deerfield, USA.
David G HallDepartment of Investigative Pathology, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, 46285, IN, USA.
David E WatsonDepartment of Investigative Toxicology, Non Clinical Safety Assessment and Pathology, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, 46285, IN, USA.
Eli Lilly (United States) · USTakeda (United States) · USKelly Services (United States) · USMaastricht University · NLNational Institute of Environmental Health Sciences · US

Funding

Microarray and Genome InformaticsZIAES102345 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI BUSHEL, ROBERT · 2009 to 2021
$10.8M
6 · The paper itself

Abstract

backgroundMicroRNAs (miRNA) are ~19-25 nucleotide long RNA molecules that fine tune gene expression through the inhibition of translation or degradation of the mRNA through incorporation into the RNA induced silencing complex (RISC). MicroRNAs are stable in the serum and plasma, are detectable in a wide variety of body fluids, are conserved across veterinary species and humans and are expressed in a tissue specific manner. They can be detected at low concentrations in circulation in animals and humans, generating interest in the utilization of miRNAs as serum and/or plasma based biomarkers of tissue injury. MicroRNA tissue profiling in rodents has been published, but sample an insufficient number of organs of toxicologic interest using microarray or qPCR technologies for miRNA detection. Here we impart an improved rat microRNA body atlas consisting of 21 and 23 tissues of toxicologic interest from male and female Sprague Dawley rats respectively, using Illumina miRNA sequencing. Several of the authors created a dog miRNA body atlas and we collaborated to test miRNAs conserved in rat and dog pancreas in caerulein toxicity studies utilizing both species.

resultsA rich data set is presented that more robustly defines the tissue specificity and enrichment profiles of previously published and undiscovered rat miRNAs. We generated 1,927 sequences that mapped to mature miRNAs in rat, mouse and human from miRBase and discovered an additional 1,162 rat miRNAs as compared to the current number of rat miRNAs in miRBase version 21. Tissue specific and enriched miRNAs were identified and a subset of these miRNAs were validated by qPCR for tissue specificity or enrichment. As an example of the power of this approach, we have conducted rat and dog pancreas toxicity studies and examined the levels of some tissue specific and enriched miRNAs conserved between rat and dog in the serum of each species. The studies demonstrate that conserved tissue specific/enriched miRs-216a-5p, 375-3p, 148a-3p, 216b-5p and 141-3p are candidate biomarkers of pancreatic injury in the rat and dog.

conclusionsA microRNA body atlas for rat and dog was useful in identifying new candidate miRNA biomarkers of organ toxicity in 2 toxicologically relevant species.

Indexed as

BiomarkersAnimalsDogsFemaleGene ExpressionGene Expression ProfilingHigh-Throughput Nucleotide SequencingHumansMaleMiceMicroRNAsOrgan SpecificityPancreasRatsTissue DistributionBiomarkersMicroRNAsBiomarkersDeep sequencingmicroRNAPancreatic toxicityTissue enrichedTissue specific

Identifiers

PMID27576563
PMCPMC5006322
OpenAlexW2518568673

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.