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Long non-coding RNA NEAT1 is a transcriptional target of p53 and modulates p53-induced transactivation and

Masashi Idogawa1,2, Tomoko Ohashi1,3, Yasushi Sasaki1,2

  • 1Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.

International Journal of Cancer
|March 16, 2017
PubMed

Insights

The tumor suppressor p53 directly targets the long non-coding RNA NEAT1. NEAT1 induction by p53 aids tumor suppression, suggesting a critical p53-NEAT1 network in cancer.

Area of Science:

  • Molecular Biology
  • Cancer Genetics
  • Non-coding RNA Research

Background:

  • The tumor suppressor p53 plays a crucial role in preventing cancer by regulating gene expression.
  • Understanding p53's direct transcriptional targets is key to elucidating its tumor-suppressive functions.
  • While protein-coding genes have been extensively studied, the role of long non-coding RNAs (lncRNAs) as p53 targets is an emerging area.

Purpose of the Study:

  • To identify novel direct transcriptional targets of p53, focusing on lncRNAs.
  • To investigate the functional role of the lncRNA NEAT1 in p53-mediated tumor suppression.
  • To explore the relationship between NEAT1 expression, p53 activity, and cancer prognosis.

Main Methods:

  • Analysis of next-generation chromatin immunoprecipitation-sequencing (ChIP-seq) data for p53 binding.
  • Experimental validation of NEAT1 as a direct transcriptional target of p53.
  • Assessment of NEAT1's impact on cancer cell growth and gene transactivation.
  • Correlation analysis between NEAT1 expression levels and patient prognosis in various cancers.

Main Results:

  • The lncRNA NEAT1 was identified as a direct transcriptional target of p53 using ChIP-seq data.
  • Suppression of NEAT1 induction by p53 was found to reduce p53's inhibitory effect on cancer cell growth.
  • NEAT1 modulates gene transactivation, including that of other lncRNAs.
  • Low expression of NEAT1 is significantly associated with poor prognosis in several types of cancer.

Conclusions:

  • NEAT1 induction is a critical component of the tumor-suppressor function of p53.
  • The p53-NEAT1 axis represents a novel transcriptional network involved in diverse biological functions and tumor suppression.
  • NEAT1 may serve as a potential biomarker for cancer prognosis and a therapeutic target.
Keywords:
NEAT1lncRNAp53transcriptional regulation

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