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Tumor suppressor p53 induces miR-1915 processing to inhibit Bcl-2 in the apoptotic response to DNA damage

Kazuya Nakazawa1, Nurmaa Dashzeveg, Kiyotsugu Yoshida

  • 1Department of Biochemistry, The Jikei University School of Medicine, Tokyo, Japan; Medical Research Institute, Tokyo Medical and Dental University, Japan.

The FEBS Journal
|May 13, 2014
PubMed

Insights

The tumor suppressor p53 regulates miR-1915 processing in response to DNA damage. This mechanism controls the expression of the antiapoptotic protein Bcl-2, impacting cancer drug resistance.

Area of Science:

  • Molecular biology
  • Cancer research
  • Gene regulation

Background:

  • The antiapoptotic protein Bcl-2 is overexpressed in cancers, contributing to drug resistance.
  • The tumor suppressor p53 normally downregulates Bcl-2 following DNA damage, but the mechanism is unclear.
  • MicroRNA miR-1915 has been implicated in repressing Bcl-2 in colorectal cancer cells.

Purpose of the Study:

  • To elucidate the molecular mechanism by which p53 negatively regulates Bcl-2 expression.
  • To investigate the role of miR-1915 in the p53-mediated regulation of Bcl-2.
  • To understand the link between p53, miR-1915, and cancer drug resistance.

Main Methods:

  • Investigated p53's effect on miR-1915 expression in response to DNA damage.
  • Analyzed the impact of p53 induction on different forms of miR-1915 (primary, precursor, mature).
  • Assessed the effect of miR-1915 inhibition on Bcl-2 expression after genotoxic treatment.

Main Results:

  • p53 induction in response to DNA damage influences the expression of precursor and mature miR-1915, but not primary miR-1915.
  • Inhibiting miR-1915 prevents the downregulation of Bcl-2 expression following genotoxin treatment.
  • p53 targets the processing of miR-1915 from its primary to precursor form.

Conclusions:

  • p53 negatively regulates Bcl-2 expression through the modulation of miR-1915 processing.
  • This novel pathway involving p53 and miR-1915 offers new insights into cancer drug resistance mechanisms.
  • Understanding this regulatory axis could lead to improved therapeutic strategies for Bcl-2-overexpressing cancers.
Keywords:
Bcl-2DNA damageapoptosismiR-1915p53

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