Long non-coding RNA TILR constitutively represses TP53 and apoptosis in lung cancer

Mika Iwai1, Taisuke Kajino1,2, Masahiro Nakatochi3

  • 1Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.

Oncogene
|December 15, 2022
PubMed

Insights

A novel long non-coding RNA, TP53-inhibiting lncRNA (TILR), suppresses p53 expression in lung cancer. TILR, with PCBP2, maintains low p53 activity, preventing unnecessary apoptosis.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • RNA Biology

Background:

  • Non-coding RNAs play crucial roles in lung cancer development.
  • The precise regulatory mechanisms involving non-coding RNAs and tumor suppressors like p53 are not fully understood.

Purpose of the Study:

  • To identify and characterize novel non-coding RNAs involved in lung cancer regulation.
  • To elucidate the function of a newly discovered lncRNA, TP53-inhibiting lncRNA (TILR), in controlling p53 expression.

Main Methods:

  • Proteomic analysis to identify TILR-interacting proteins.
  • RNA binding assays to determine TILR's interaction with p53 mRNA.
  • Gene silencing experiments (siRNA) to assess the functional impact of TILR and PCBP2.
  • Analysis of downstream gene expression and apoptosis induction.

Main Results:

  • Identification of a novel long non-coding RNA, TP53-inhibiting lncRNA (TILR).
  • TILR acts as a negative regulator of p53 expression, affecting p21 and MDM2.
  • TILR binds to p53 mRNA via PCBP2, suppressing p53 post-transcriptionally.
  • TILR influences p53 and Fanconi anemia pathway genes, creating a feedback loop.

Conclusions:

  • TILR constitutively inhibits p53 expression in conjunction with PCBP2.
  • This inhibition maintains low p53 transcriptional activity, preventing spurious apoptosis.
  • TILR represents a potential therapeutic target in lung cancer.

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