Evidence map›Paper›PMID 26001595›Full record

ArticleTranslational research : the journal of laboratory and clinical medicine2015

High-throughput sequencing reveals altered expression of hepatic microRNAs in nonalcoholic fatty liver disease-related fibrosis.

Fatjon Leti, Ivana Malenica, Meera Doshi, Amanda Courtright, Kendall Van Keuren-Jensen, Christophe Legendre, Christopher D Still, Glenn S Gerhard, Johanna K DiStefano

Open access · greenAbstract read
In one paragraph

Article in Translational research : the journal of laboratory and clinical medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 1 pooled it
7.0field-weighted citation impact, top 2% 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

49 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.

  1. Pooled it
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  18. MicroRNAs in the Pathogenesis of Nonalcoholic Fatty Liver Disease.International journal of biological sciences · 2021
    Review
  19. Review
  20. miR‑148a‑3p regulates alcoholic liver fibrosis through targeting ERBB3.International journal of molecular medicine · 2020
    Article
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

9 authors at 2 institutions in 1 country.

Fatjon LetiDivision of Diabetes, Cardiovascular and Metabolic Diseases, Translational Genomics Research Institute, Phoenix, Ariz.
Ivana MalenicaDivision of Diabetes, Cardiovascular and Metabolic Diseases, Translational Genomics Research Institute, Phoenix, Ariz.
Meera DoshiDivision of Diabetes, Cardiovascular and Metabolic Diseases, Translational Genomics Research Institute, Phoenix, Ariz.
Amanda CourtrightDivision of Diabetes, Cardiovascular and Metabolic Diseases, Translational Genomics Research Institute, Phoenix, Ariz.
Kendall Van Keuren-JensenDivision of Diabetes, Cardiovascular and Metabolic Diseases, Translational Genomics Research Institute, Phoenix, Ariz.
Christophe LegendreDivision of Diabetes, Cardiovascular and Metabolic Diseases, Translational Genomics Research Institute, Phoenix, Ariz.
Christopher D StillDepartment of Gastroenterology and Nutrition, Geisinger Obesity Institute, Danville, PA.
Glenn S GerhardDepartment of Biochemistry and Molecular Biology, Temple University School of Medicine, Philadelphia, PA.
Johanna K DiStefanoDivision of Diabetes, Cardiovascular and Metabolic Diseases, Translational Genomics Research Institute, Phoenix, Ariz. Electronic address: jdistefano@tgen.org.
Translational Genomics Research Institute · USGeisinger Health System · US

Funding

Genetic determinants of NAFLD severity and progressionR01DK091601 · NIDDK · TRANSLATIONAL GENOMICS RESEARCH INST · PI DISTEFANO, JOHANNA K, GERHARD, GLENN S · 2011 to 2015
$2.9M
NIDDK NIH HHS DK091601NIDDK NIH HHS R01 DK091601
6 · The paper itself

Abstract

Recent evidence suggests that microRNAs (miRNAs), small, noncoding RNA molecules that regulate gene expression, may play a role in the regulation of metabolic disorders, including nonalcoholic fatty liver disease (NAFLD). To identify miRNAs that mediate NAFLD-related fibrosis, we used high-throughput sequencing to assess miRNAs obtained from liver biopsies of 15 individuals without NAFLD fibrosis (F0) and 15 individuals with severe NAFLD fibrosis or cirrhosis (F3-F4), matched for age, sex, body mass index, type 2 diabetes status, hemoglobin A1c, and use of diabetes medications. We used DESeq2 and Kruskal-Wallis test to identify miRNAs that were differentially expressed between NAFLD patients with or without fibrosis, adjusting for multiple testing using Bonferroni correction. We identified a total of 75 miRNAs showing statistically significant evidence (adjusted P value <0.05) for differential expression between the 2 groups, including 30 upregulated and 45 downregulated miRNAs. Quantitative reverse-transcription polymerase chain reaction analysis of selected miRNAs identified by sequencing validated 9 of 11 of the top differentially expressed miRNAs. We performed functional enrichment analysis of dysregulated miRNAs and identified several potential gene targets related to NAFLD-related fibrosis including hepatic fibrosis, hepatic stellate cell activation, transforming growth factor beta signaling, and apoptosis signaling. We identified forkhead box O3 and F-box WD repeat domain containing 7, E3 ubiquitin protein ligase (FBXW7) as potential targets of miR-182, and found that levels of forkhead box O3, but not FBXW7, were significantly decreased in fibrotic samples. These findings support a role for hepatic miRNAs in the pathogenesis of NAFLD-related fibrosis and yield possible new insight into the molecular mechanisms underlying the initiation and progression of liver fibrosis and cirrhosis.

Indexed as

DemographyDown-RegulationFemaleGene Expression ProfilingHigh-Throughput Nucleotide SequencingHumansLiverLiver CirrhosisMaleMicroRNAsMiddle AgedNon-alcoholic Fatty Liver DiseaseReal-Time Polymerase Chain ReactionReproducibility of ResultsRNA, MessengerUp-RegulationMicroRNAsRNA, Messenger

Identifiers

PMID26001595
PMCPMC4537840
OpenAlexW1825697469

What OpenQuestion holds

Textmetadata
LicenceTDM
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.