Evidence map›Paper›PMID 22747855›Full record

ArticleMolecular cancer2012

Silencing of a large microRNA cluster on human chromosome 14q32 in melanoma: biological effects of mir-376a and mir-376c on insulin growth factor 1 receptor.

Liron Zehavi, Roi Avraham, Aviv Barzilai, Dalia Bar-Ilan, Roy Navon, Yechezkel Sidi, Dror Avni, Raya Leibowitz-Amit

Open access · goldAbstract read
In one paragraph

Article in Molecular cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed, 3 pooled it
3.4field-weighted citation impact, top 8% 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

83 citing papers in PubMed, 3 syntheses or guidelines pooled it, 135 citations in OpenAlex.

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  20. Cellular microRNA-127-3p suppresses oncogenic herpesvirus-induced transformation and tumorigenesis via down-regulation of SKP2.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article

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

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 2 institutions in 1 country.

Liron ZehaviLaboratory of Molecular Cell Biology, Cancer Research Center and Department of Medicine C, Sheba Medical Center, Tel Hashomer, Israel.
Roi Avraham
Aviv Barzilai
Dalia Bar-Ilan
Roy Navon
Yechezkel Sidi
Dror Avni
Raya Leibowitz-Amit
Sheba Medical Center · ILWeizmann Institute of Science · IL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMetastatic melanoma is a devastating disease with limited therapeutic options. MicroRNAs (miRNAs) are small non coding RNA molecules with important roles in post-transcriptional gene expression regulation, whose aberrant expression has been implicated in cancer.

resultsWe show that the expression of miRNAs from a large cluster on human chromosome 14q32 is significantly down-regulated in melanoma cell lines, benign nevi and melanoma samples relative to normal melanocytes. This miRNA cluster resides within a parentally imprinted chromosomal region known to be important in development and differentiation. In some melanoma cell lines, a chromosomal deletion or loss-of-heterozygosity was observed in the cis-acting regulatory region of this cluster. In several cell lines we were able to re-express two maternally-induced genes and several miRNAs from the cluster with a combination of de-methylating agents and histone de-acetylase inhibitors, suggesting that epigenetic modifications take part in their silencing. Stable over-expression of mir-376a and mir-376c, two miRNAs from this cluster that could be re-expressed following epigenetic manipulation, led to modest growth retardation and to a significant decrease in migration in-vitro. Bioinformatic analysis predicted that both miRNAs could potentially target the 3'UTR of IGF1R. Indeed, stable expression of mir-376a and mir-376c in melanoma cells led to a decrease in IGF1R mRNA and protein, and a luciferase reporter assay indicated that the 3'UTR of IGF1R is a target of both mir-376a and mir-376c.

conclusionsOur work is the first to show that the large miRNA cluster on chromosome 14q32 is silenced in melanoma. Our results suggest that down-regulation of mir-376a and mir-376c may contribute to IGF1R over-expression and to aberrant negative regulation of this signaling pathway in melanoma, thus promoting tumorigenesis and metastasis.

Indexed as

Chromosomes, Human, Pair 14Gene SilencingMultigene FamilyAcetylationBase SequenceCell Line, TumorCell MovementCell ProliferationCluster AnalysisDNA Copy Number VariationsEpigenomicsGene Expression ProfilingGene Expression Regulation, NeoplasticGene OrderGenomic ImprintingHistonesHistonesMicroRNAsMIRN376C microRNA, humanReceptor, IGF Type 1

Identifiers

PMID22747855
PMCPMC3444916
OpenAlexW2139443896

What OpenQuestion holds

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LicenceCC BY
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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.