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RNA-Binding Protein FXR1 Regulates p21 and TERC RNA to Bypass p53-Mediated Cellular Senescence in OSCC

Mrinmoyee Majumder1, Reniqua House1, Nallasivam Palanisamy2

  • 1Department of Oral Health Sciences and Center for Oral Health Research, College of Dental Medicine, Medical University of South Carolina, Charleston, South Carolina, United States of America.

Plos Genetics
|September 9, 2016
PubMed

Insights

Fragile X-related protein 1 (FXR1) prevents cellular senescence in oral cancer by regulating p21 mRNA and Telomerase RNA Component (TERC). Silencing FXR1 triggers senescence, inhibiting cancer cell proliferation.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Gene Regulation

Background:

  • RNA-binding proteins (RBPs) control gene expression post-transcriptionally.
  • Cellular senescence is a critical tumor suppressor mechanism.
  • Dysregulation of RBPs contributes to cancer development.

Purpose of the Study:

  • To investigate the role of fragile X-related protein 1 (FXR1) in regulating cellular senescence in cancer.
  • To elucidate the molecular mechanisms by which FXR1 influences senescence pathways.
  • To determine the therapeutic potential of targeting FXR1 in oral cancer.

Main Methods:

  • Quantitative PCR and Western blotting to assess gene and protein expression.
  • RNA immunoprecipitation (RIP) assays to identify FXR1 RNA targets.
  • Cell viability and colony formation assays to evaluate proliferation and senescence.

Main Results:

  • Overexpressed FXR1 targets p21 mRNA and Telomerase RNA Component (TERC) RNA, regulating their turnover.
  • FXR1 silencing in oral cancer cells induces p53 activation, DNA damage, and cellular senescence.
  • FXR1 binds and destabilizes p21 mRNA, reducing p21 protein, and stabilizes TERC RNA, potentially suppressing senescence via telomerase.

Conclusions:

  • FXR1 plays a crucial role in bypassing cellular senescence in oral cancer through p53-dependent regulation of p21.
  • FXR1-mediated suppression of senescence is irreversible, leading to a loss of proliferative capacity in cancer cells.
  • FXR1 represents a novel therapeutic target for reactivating senescence and inhibiting oral cancer progression.

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