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Interdependent regulation of p53 and miR-34a in chronic lymphocytic leukemia

Olaf Merkel1, Daniela Asslaber, Josefina D Piñón

  • 1Laboratory for Immunological and Molecular Cancer Research, IIIrd Medical Department with Hematology, Medical Oncology, Hemostaseology, Rheumatology and Infectiology of the Paracelsus Medical University Salzburg, Salzburg, Austria. o.merkel@salk.at

Cell Cycle (Georgetown, Tex.)
|June 29, 2010
PubMed

Insights

MicroRNA-34a (miR-34a) is elevated in chronic lymphocytic leukemia (CLL) and linked to shorter treatment times. Its apoptosis-inducing effect in CLL cells depends on the p53 pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Chronic lymphocytic leukemia (CLL) incidence is 4/100,000, with deregulated microRNA (miRNA) expression noted.
  • MicroRNAs are small, non-coding RNAs regulating protein expression by targeting 3'-UTR regions.
  • The miR-34 family, induced by p53, mediates tumor suppressor functions like apoptosis and cell cycle arrest.

Purpose of the Study:

  • Investigate the role of miR-34a in CLL.
  • Determine the relationship between miR-34a expression, SNP309, and treatment time in CLL.
  • Assess the functional impact of miR-34a reintroduction and p53 pathway integrity in CLL cells.

Main Methods:

  • Analysis of miR-34a expression in a TCL1-mouse model of CLL and human CLL samples.
  • Correlation of miR-34a expression with SNP309 in the MDM2 gene promoter.
  • Assessment of miR-34a's effect on apoptosis in CLL cells and p53-knockdown HCT-116 cells.

Main Results:

  • miR-34a is significantly increased in both mouse and human CLL.
  • miR-34a expression is linked to SNP309 and inversely correlated with time to treatment in CLL.
  • Reintroduction of miR-34a induces apoptosis in CLL cells, dependent on an intact p53 pathway.

Conclusions:

  • miR-34a is a key player in CLL pathogenesis.
  • miR-34a expression levels and their dependence on p53 activity can serve as prognostic markers in CLL.
  • miR-34a is proposed as a marker for p53 pathway activity in CLL.

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