Evidence map›Paper›PMID 26206264›Full record

ArticleBMC cancer2015

Functional microRNA high throughput screening reveals miR-9 as a central regulator of liver oncogenesis by affecting the PPARA-CDH1 pathway.

Alexandra Drakaki, Maria Hatziapostolou, Christos Polytarchou, Christina Vorvis, George A Poultsides, John Souglakos, Vassilis Georgoulias, Dimitrios Iliopoulos

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 7% 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

41 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.

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  13. Non-coding RNA crosstalk with nuclear receptors in liver disease.Biochimica et biophysica acta. Molecular basis of disease · 2021
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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

8 authors at 4 institutions in 2 countries.

Alexandra DrakakiDivision of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. adrakaki@mednet.ucla.edu.
Maria HatziapostolouCenter for Systems Biomedicine, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, 650 Charles E. Young Dr., CHS 44-133, Los Angeles, CA, 90095-7278, USA. MHatziapostolou@mednet.ucla.edu.
Christos PolytarchouCenter for Systems Biomedicine, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, 650 Charles E. Young Dr., CHS 44-133, Los Angeles, CA, 90095-7278, USA. cpolytarchou@mednet.ucla.edu.
Christina VorvisCenter for Systems Biomedicine, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, 650 Charles E. Young Dr., CHS 44-133, Los Angeles, CA, 90095-7278, USA. cvorvis@ucla.edu.
George A PoultsidesDepartment of Surgery, Stanford School of Medicine, Stanford University, Palo Alto, CA, USA. gpoultsides@stanford.edu.
John SouglakosLaboratory of Tumor Biology, Department of Medical Oncology, University Hospital of Heraklion, Heraklion, Crete, Greece. johnsougl@gmail.com.
Vassilis GeorgouliasLaboratory of Tumor Biology, Department of Medical Oncology, University Hospital of Heraklion, Heraklion, Crete, Greece. georgouliasv@gmail.com.
Dimitrios IliopoulosCenter for Systems Biomedicine, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, 650 Charles E. Young Dr., CHS 44-133, Los Angeles, CA, 90095-7278, USA. diliopoulos@mednet.ucla.edu.
University of California, Los Angeles · USUniversity Hospital of Heraklion · GRCharles R. Drew University of Medicine and Science · USStanford Medicine · US

Funding

Pilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0M
NIDDK NIH HHS P30 DK041301
6 · The paper itself

Abstract

backgroundHepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths, reflecting the aggressiveness of this type of cancer and the absence of effective therapeutic regimens. MicroRNAs have been involved in the pathogenesis of different types of cancers, including liver cancer. Our aim was to identify microRNAs that have both functional and clinical relevance in HCC and examine their downstream signaling effectors.

methodsMicroRNA and gene expression levels were measured by quantitative real-time PCR in HCC tumors and controls. A TargetScan algorithm was used to identify miR-9 downstream direct targets.

resultsA high-throughput screen of the human microRNAome revealed 28 microRNAs as regulators of liver cancer cell invasiveness. MiR-9, miR-21 and miR-224 were the top inducers of HCC invasiveness and also their expression was increased in HCC relative to control liver tissues. Integration of the microRNA screen and expression data revealed miR-9 as the top microRNA, having both functional and clinical significance. MiR-9 levels correlated with HCC tumor stage and miR-9 overexpression induced SNU-449 and HepG2 cell growth, invasiveness and their ability to form colonies in soft agar. Bioinformatics and 3'UTR luciferase analyses identified E-cadherin (CDH1) and peroxisome proliferator-activated receptor alpha (PPARA) as direct downstream effectors of miR-9 activity. Inhibition of PPARA suppressed CDH1 mRNA levels, suggesting that miR-9 regulates CDH1 expression directly through binding in its 3'UTR and indirectly through PPARA. On the other hand, miR-9 inhibition of overexpression suppressed HCC tumorigenicity and invasiveness. PPARA and CDH1 mRNA levels were decreased in HCC relative to controls and were inversely correlated with miR-9 levels.

conclusionsTaken together, this study revealed the involvement of the miR-9/PPARA/CDH1 signaling pathway in HCC oncogenesis.

Indexed as

3' Untranslated RegionsAntigens, CDCadherinsCarcinoma, HepatocellularCell Line, TumorCell MovementComputational BiologyGene Expression ProfilingGene Expression Regulation, NeoplasticHep G2 CellsHigh-Throughput Screening AssaysHumansLiver NeoplasmsMicroRNAsPPAR alphaSignal Transduction3' Untranslated RegionsAntigens, CDCadherinsCDH1 protein, humanMicroRNAsMIRN92 microRNA, humanPPAR alpha

Identifiers

PMID26206264
PMCPMC4512159
OpenAlexW1568687554

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.