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Neat1 is a p53-inducible lincRNA essential for transformation suppression

Stephano S Mello1, Carolyn Sinow1, Nitin Raj1

  • 1Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California 94305, USA.

Genes & Development
|July 13, 2017
PubMed

Insights

The tumor suppressor p53 regulates the noncoding RNA Neat1, which is crucial for preventing cell transformation and cancer initiation. Neat1 is not essential for apoptosis but plays a key role in suppressing oncogene-induced neoplasia.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The p53 gene is frequently mutated in cancers, highlighting its role as a tumor suppressor.
  • Identifying p53-regulated genes critical for tumor suppression is essential for understanding cancer development.
  • The noncoding genome's role in p53-mediated tumor suppression is largely unexplored.

Purpose of the Study:

  • To identify novel p53 target genes within the noncoding genome.
  • To investigate the functional role of the noncoding RNA Neat1 in p53-mediated tumor suppression.
  • To elucidate the mechanisms by which Neat1 influences transformation and cancer initiation.

Main Methods:

  • Utilized p53 ChIP-seq and RNA-seq data to identify p53 target genes.
  • Examined Neat1's function in Neat1-deficient mouse fibroblasts and KrasG12D-expressing mice.
  • Analyzed gene expression changes in response to Neat1 loss.

Main Results:

  • Identified Neat1, a noncoding RNA, as a novel p53 target gene induced by various stress signals.
  • Neat1 is dispensable for p53-mediated cell cycle arrest and apoptosis but crucial for suppressing oncogene-induced transformation.
  • Neat1 deficiency enhances fibroblast transformation and promotes premalignant lesions in mice, associated with global gene expression changes.

Conclusions:

  • Neat1 is a p53-regulated lincRNA that plays a critical role in suppressing cellular transformation and cancer initiation.
  • This study provides new insights into p53-mediated tumor suppression by highlighting the role of a noncoding RNA.
  • Neat1's function in preventing neoplasia offers a potential new avenue for cancer research.
Keywords:
Neat1lincRNAp53pancreatic cancertumor suppression

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