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A new lncRNA, APTR, associates with and represses the CDKN1A/p21 promoter by recruiting polycomb proteins

Masamitsu Negishi1, Somsakul P Wongpalee1, Sukumar Sarkar1

  • 1Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.

Plos One
|April 22, 2014
PubMed

Insights

A novel long noncoding RNA, APTR, promotes cell proliferation by repressing CDKN1A/p21. APTR targets the p21 promoter via an Alu sequence and recruits PRC2 for epigenetic repression, impacting glioblastoma progression.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Epigenetics

Background:

  • Long noncoding RNAs (lncRNAs) regulate cell physiology, yet many lack defined functions.
  • CDKN1A/p21 is a key cell-cycle inhibitor, DNA damage response regulator, and tumor suppressor effector, crucial in cancer.
  • Understanding lncRNA roles in tumor progression is vital for developing new therapeutic strategies.

Purpose of the Study:

  • To identify novel lncRNAs regulating cell proliferation and tumor progression.
  • To elucidate the mechanism by which APTR influences CDKN1A/p21 expression.
  • To investigate the role of APTR in human cancers, specifically glioblastomas.

Main Methods:

  • siRNA screening of human lncRNAs to identify proliferation regulators.
  • Assays to determine APTR's interaction with the CDKN1A/p21 promoter.
  • Chromatin immunoprecipitation to assess Polycomb repressive complex 2 (PRC2) recruitment.
  • Analysis of APTR and p21 expression in glioblastoma patient samples.

Main Results:

  • A novel lncRNA, APTR, was identified as a repressor of CDKN1A/p21, promoting cell proliferation.
  • APTR utilizes a complementary-Alu sequence for promoter association and recruits PRC2 for epigenetic silencing of p21.
  • APTR downregulation is required for p21 induction following DNA damage or heat stress.
  • APTR and p21 levels are inversely correlated in human glioblastomas.

Conclusions:

  • APTR functions as a proliferative factor by epigenetically repressing the cell-cycle inhibitor CDKN1A/p21.
  • Alu elements within lncRNAs can mediate targeted promoter interactions for gene regulation.
  • APTR represents a potential therapeutic target for cancers exhibiting high proliferation rates.

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