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The mutant p53-ID4 complex controls VEGFA isoforms by recruiting lncRNA MALAT1

Magdalena Pruszko1,2, Elisa Milano3, Mattia Forcato4

  • 1Department of Molecular Biology, International Institute of Molecular and Cell Biology in Warsaw, Warsaw, Poland.

EMBO Reports
|June 28, 2017
PubMed

Insights

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) interacts with mutant p53 and ID4 proteins, altering VEGFA isoform expression in aggressive breast cancer. This highlights MALAT1

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non-coding RNA (lncRNA), is linked to aggressive mammary carcinomas.
  • MALAT1 localizes to nuclear speckles and influences splicing factor activity.

Purpose of the Study:

  • To investigate the role of MALAT1 in breast cancer cells with mutant p53 and ID4.
  • To elucidate the mechanism by which MALAT1 affects VEGFA isoform expression.

Main Methods:

  • Investigated protein-RNA interactions using immunoprecipitation and chromatin association assays.
  • Analyzed VEGFA pre-mRNA splicing and isoform expression.
  • Correlated gene expression signatures with specific mutations in breast cancer subtypes.

Main Results:

  • Oncogenic splicing factor SRSF1 bridges MALAT1 to mutant p53 and ID4.
  • Mutant p53 and ID4 cause MALAT1 delocalization and chromatin association.
  • MALAT1 is aberrantly recruited to VEGFA pre-mRNA, modulating its isoforms.
  • VEGFA expression signatures associate with ID4 and TP53 mutations in basal-like breast cancer.

Conclusions:

  • MALAT1 plays a critical role in controlling VEGFA isoform expression in breast cancer cells harboring mutant p53 and ID4.
  • This interaction highlights a novel regulatory pathway in aggressive breast cancer phenotypes.
Keywords:
ID4MALAT1SRSF1VEGFAmutant p53

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