Evidence map›Paper›PMID 25024357›Full record

ArticleRNA (New York, N.Y.)2014

Reproducible combinatorial regulatory networks elucidate novel oncogenic microRNAs in non-small cell lung cancer.

Ramkrishna Mitra, Mick D Edmonds, Jingchun Sun, Min Zhao, Hui Yu, Christine M Eischen, Zhongming Zhao

Open access · bronzeAbstract read
In one paragraph

Article in RNA (New York, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
2.4field-weighted citation impact, top 12% 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

39 citing papers in PubMed, 50 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

7 authors at 1 institution in 1 country.

Ramkrishna MitraDepartment of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Mick D EdmondsDepartment of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Jingchun SunDepartment of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Min ZhaoDepartment of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Hui YuDepartment of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Christine M EischenDepartment of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Zhongming ZhaoDepartment of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee 37212, USA Center for Quantitative Sciences, Vanderbilt University, Nashville, Tennessee 37232, USA.
Vanderbilt University · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
The Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4M
Understanding and Controlling p120 Dysfunction in CRCP50CA095103 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI COFFEY, ROBERT J. · 2002 to 2017
$33.6M
TARGETING NOTCH 3 IN LUNG CANCERP50CA090949 · NCI · VANDERBILT UNIVERSITY · PI MASSION, PIERRE P. · 2001 to 2011
$24.1M
Integrated Biological Systems Training in OncologyT32CA119925 · NCI · VANDERBILT UNIVERSITY · PI Vivian Gama, William Patrick Tansey · 2008 to 2026
$7.6M
Mapping the Genetic Architecture of Complex Disease via RNA-seq and GWAS DataR01LM011177 · NLM · VANDERBILT UNIVERSITY · PI WANG, LILY, ZHAO, ZHONGMING · 2012 to 2014
$1.0M
Investigating MicroRNAs and Their Regulatory Networks in GlioblastomaR03CA167695 · NCI · VANDERBILT UNIVERSITY · PI ZHAO, ZHONGMING · 2013 to 2014
$154k
NCATS NIH HHS UL1 TR000445NCATS NIH HHS UL1TR000445NCI NIH HHS P30 CA068485NCI NIH HHS P30CA68485NCI NIH HHS P50 CA090949NCI NIH HHS P50CA090949NCI NIH HHS P50 CA095103NCI NIH HHS P50CA095103NCI NIH HHS R03 CA167695NCI NIH HHS R03CA167695NCI NIH HHS T32 CA119925NLM NIH HHS R01 LM011177NLM NIH HHS R01LM011177
6 · The paper itself

Abstract

While previous studies reported aberrant expression of microRNAs (miRNAs) in non-small cell lung cancer (NSCLC), little is known about which miRNAs play central roles in NSCLC's pathogenesis and its regulatory mechanisms. To address this issue, we presented a robust computational framework that integrated matched miRNA and mRNA expression profiles in NSCLC using feed-forward loops. The network consists of miRNAs, transcription factors (TFs), and their common predicted target genes. To discern the biological meaning of their associations, we introduced the direction of regulation. A network edge validation strategy using three independent NSCLC expression profiling data sets pinpointed reproducible biological regulations. Reproducible regulation, which may reflect the true molecular interaction, has not been applied to miRNA-TF co-regulatory network analyses in cancer or other diseases yet. We revealed eight hub miRNAs that connected to a higher proportion of targets validated by independent data sets. Network analyses showed that these miRNAs might have strong oncogenic characteristics. Furthermore, we identified a novel miRNA-TF co-regulatory module that potentially suppresses the tumor suppressor activity of the TGF-β pathway by targeting a core pathway molecule (TGFBR2). Follow-up experiments showed two miRNAs (miR-9-5p and miR-130b-3p) in this module had increased expression while their target gene TGFBR2 had decreased expression in a cohort of human NSCLC. Moreover, we demonstrated these two miRNAs directly bind to the 3' untranslated region of TGFBR2. This study enhanced our understanding of miRNA-TF co-regulatory mechanisms in NSCLC. The combined bioinformatics and validation approach we described can be applied to study other types of diseases.

Indexed as

Gene Regulatory NetworksOncogenesCarcinoma, Non-Small-Cell LungComputational BiologyGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, NeoplasmHumansLung NeoplasmsMicroRNAsReproducibility of ResultsSystems IntegrationTranscription FactorsMicroRNAsTranscription Factorsfeed-forward looplung cancermicroRNAregulatory networktranscription factor

Identifiers

PMID25024357
PMCPMC4138319
OpenAlexW2003048639

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.