Evidence map›Paper›PMID 34709752›Full record

ArticleClinical and translational medicine2021

Interleukin enhancer-binding factor 2 promotes cell proliferation and DNA damage response in metastatic melanoma.

Xiaoqing Zhang, Matias A Bustos, Rebecca Gross, Romela Irene Ramos, Teh-Ling Takeshima, Gordon B Mills, Qiang Yu, Dave S B Hoon

Open access · goldAbstract read
In one paragraph

Article in Clinical and translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

18 citing papers in PubMed, 25 citations in OpenAlex.

  1. Cells · 2026
    Article
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  5. Facts and Hopes: Toward the Next Quantum Leap in Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Review
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  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. The 1q21.3 region driver geneTranslational cancer research · 2022
    Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. 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

8 authors at 3 institutions in 2 countries.

Xiaoqing ZhangDepartment of Translational Molecular Medicine, Providence Saint John's Health Center, Saint John's Cancer Institute, Santa Monica, California.
Matias A BustosDepartment of Translational Molecular Medicine, Providence Saint John's Health Center, Saint John's Cancer Institute, Santa Monica, California.
Rebecca GrossDepartment of Translational Molecular Medicine, Providence Saint John's Health Center, Saint John's Cancer Institute, Santa Monica, California.
Romela Irene RamosDepartment of Translational Molecular Medicine, Providence Saint John's Health Center, Saint John's Cancer Institute, Santa Monica, California.
Teh-Ling TakeshimaDepartment of Translational Molecular Medicine, Providence Saint John's Health Center, Saint John's Cancer Institute, Santa Monica, California.
Gordon B MillsDepartment of Cell Development and Cancer Biology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon.
Qiang YuAgency for Science Technology and Research (A*STAR), Genome Institute of Singapore, Biopolis, Singapore.
Dave S B HoonDepartment of Translational Molecular Medicine, Providence Saint John's Health Center, Saint John's Cancer Institute, Santa Monica, California.ORCID 0000-0003-1915-3683
Saint John's Health Center · USAgency for Science, Technology and Research · SGOregon Health & Science University · US

Funding

Multiphoton Microscope for Deep Tissue ImagingS10OD025017 · OD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BENTOLILA, LAURENT A. · 2018 to 2018
$599k
NIH HHS S10 OD025017
6 · The paper itself

Abstract

background1q21.3 amplification, which is frequently observed in metastatic melanoma, is associated with cancer progression. Interleukin enhancer-binding factor 2 (ILF2) is located in the 1q21.3 amplified region, but its functional role or contribution to tumour aggressiveness in cutaneous melanoma is unknown.

methodsIn silico analyses were performed using the TCGA SKCM dataset with clinical annotations and three melanoma microarray cohorts from the GEO datasets. RNA in situ hybridisation and immunohistochemistry were utilised to validate the gene expression in melanoma tissues. Four stable melanoma cell lines were established for in vitro ILF2 functional characterisation.

resultsOur results showed that the ILF2 copy number variation (CNV) is positively correlated with ILF2 mRNA expression (r = 0.68, p < .0001). Additionally, ILF2 expression is significantly increased with melanoma progression (p < .0001), and significantly associated with poor overall survival for metastatic melanoma patients (p = .026). The overexpression of ILF2 (ILF2-OV) promotes proliferation in metastatic melanoma cells, whereas ILF2 knockdown decreases proliferation by blocking the cell cycle. Mechanistically, we demonstrated the interaction between ILF2 and the splicing factor U2AF2, whose knockdown reverses the proliferation effects mediated by ILF2-OV. Stage IIIB-C melanoma patients with high ILF2-U2AF2 expression showed significantly shorter overall survival (p = .024). Enhanced ILF2/U2AF2 expression promotes a more efficient DNA-damage repair by increasing RAD50 and ATM mRNA expression. Paradoxically, metastatic melanoma cells with ILF2-OV were more sensitive to ATM inhibitors.

conclusionOur study uncovered that ILF2 amplification of the 1q21.3 chromosome is associated with melanoma progression and triggers a functional downstream pathway in metastatic melanoma promoting drug resistance.

Indexed as

Cell Line, TumorCell ProliferationCells, CulturedDNA Copy Number VariationsDNA DamageHumansMelanomaNuclear Factor 45 ProteinSkin NeoplasmsNuclear Factor 45 ProteinATMDNA damage responseILF2metastatic melanomaRAD50U2AF2

Identifiers

PMID34709752
PMCPMC8516365
OpenAlexW3209610915

What Socratic 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 Socratic graph.