Evidence map›Paper›PMID 23365201›Full record

ArticleJournal of the National Cancer Institute2013

The role of miR-18b in MDM2-p53 pathway signaling and melanoma progression.

Altaf A Dar, Shahana Majid, Claudia Rittsteuer, David de Semir, Vladimir Bezrookove, Schuyler Tong, Mehdi Nosrati, Richard Sagebiel, James R Miller, Mohammed Kashani-Sabet

Open access · bronzeAbstract read
In one paragraph

Article in Journal of the National Cancer Institute, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 2 pooled it
5.1field-weighted citation impact, top 4% 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

61 citing papers in PubMed, 2 syntheses or guidelines pooled it, 118 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. How MicroRNAs Command the Battle against Cancer.International journal of molecular sciences · 2024
    Review
  12. Review
  13. Review
  14. A New Approach to Melanoma Treatment: microRNAs.Current topics in medicinal chemistry · 2024
    Review
  15. Article
  16. Role of miRNA in Melanoma Development and Progression.International journal of molecular sciences · 2022
    Review
  17. Article
  18. Article
  19. Review
  20. Article

1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Altaf A DarCenter for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, 475 Brannan St, Ste 220, San Francisco, CA 94107, USA.
Shahana Majid
Claudia Rittsteuer
David de Semir
Vladimir Bezrookove
Schuyler Tong
Mehdi Nosrati
Richard Sagebiel
James R Miller
Mohammed Kashani-Sabet
California Pacific Medical Center · USSan Francisco VA Medical Center · USUniversity of California, San Francisco · US

Funding

Validation of Genomic Targets in MelanomaR01CA114337 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KASHANI-SABET, MOHAMMED · 2005 to 2015
$3.2M
Molecular Classification of Primary Cutaneous MelanomaR01CA122947 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KASHANI-SABET, MOHAMMED · 2007 to 2011
$1.5M
NCI NIH HHS CA114337NCI NIH HHS CA122947NCI NIH HHS R01 CA114337
6 · The paper itself

Abstract

backgroundAlthough p53 is inactivated by point mutations in many tumors, melanomas infrequently harbor mutations in the p53 gene. Here we investigate the biological role of microRNA-18b (miR-18b) in melanoma by targeting the MDM2-p53 pathway.

methodsExpression of miR-18b was examined in nevi (n = 48) and melanoma (n = 92) samples and in melanoma cell lines and normal melanocytes. Immunoblotting was performed to determine the expression of various proteins regulated by miR-18b. The effects of miR-18b overexpression in melanoma cell lines were investigated using assays of colony formation, cell viability, migration, invasion, and cell cycle and in a xenograft model (n = 10 mice per group). Chromatin immunoprecipitation and methylation assays were performed to determine the mechanism of microRNA silencing.

resultsExpression of miR-18b was substantially reduced in melanoma specimens and cell lines by virtue of hypermethylation and was reinduced (by 1.5- to 5.3-fold) in melanoma cell lines after 5-AZA-deoxycytidine treatment. MDM2 was identified as a target of miR-18b action, and overexpression of miR-18b in melanoma cells was accompanied by 75% reduced MDM2 expression and 2.5-fold upregulation of p53, resulting in 70% suppression of melanoma cell colony formation. The effects of miR-18b overexpression on the p53 pathway and on melanoma cell growth were reversed by MDM2 overexpression. Stable overexpression of miR-18b produced potent tumor suppressor activity, as evidenced by suppressed melanoma cell viability, induction of apoptosis, and reduced tumor growth in vivo. miR-18b overexpression suppressed melanoma cell migration and invasiveness and reversed epithelial-to-mesenchymal transition.

conclusionsOur results demonstrate a novel role for miR-18b as a tumor suppressor in melanoma, identify the MDM2-p53 pathway as a target of miR-18b action, and suggest miR-18b overexpression as a novel strategy to reactivate the p53 pathway in human tumors.

Indexed as

Signal TransductionAntimetabolites, AntineoplasticAzacitidineBlotting, WesternCell CycleCell Line, TumorCell MovementCell SurvivalChromatin ImmunoprecipitationDNA MethylationEpithelial-Mesenchymal TransitionFlow CytometryFluorescent Antibody TechniqueGene Expression Regulation, NeoplasticGene SilencingHumansAntimetabolites, AntineoplasticAzacitidineLuciferasesMDM2 protein, humanMicroRNAsMIrn181 microRNA, humanProto-Oncogene Proteins c-mdm2Tumor Suppressor Protein p53

Identifiers

PMID23365201
PMCPMC3601951
OpenAlexW2120472737

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.