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Tumors line up for a letdown

Joshua T Mendell1

  • 1McKusick-Nathans Institute of Genetic Medicine and Department of Pediatrics and Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. jmendell@jhmi.edu

Nature Genetics
|June 27, 2009
PubMed

Insights

Cancer cells hijack a developmental pathway to suppress let-7 microRNA (miRNA) production. This mechanism, involving Lin-28 proteins, allows cancer cells to eliminate an miRNA that normally inhibits tumor growth.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cancer Research

Background:

  • MicroRNAs (miRNAs) are crucial regulators of gene expression with vital roles in normal development.
  • The let-7 miRNA family is known for its tumor-suppressive functions.
  • Lin-28 and Lin-28B are RNA-binding proteins that inhibit let-7 miRNA biogenesis during development.

Purpose of the Study:

  • To investigate whether cancer cells utilize developmental miRNA regulatory mechanisms.
  • To determine if cancer cells exploit the Lin-28/let-7 axis for their own benefit.

Main Methods:

  • Analysis of miRNA regulatory pathways in select cancer cells.
  • Investigation of the role of Lin-28 and Lin-28B proteins in cancer.
  • Examination of let-7 miRNA biogenesis inhibition in the context of cancer development.

Main Results:

  • A specific developmental mechanism for miRNA regulation was found to be co-opted by cancer cells.
  • Cancer cells utilize Lin-28 and Lin-28B RNA binding proteins to inhibit the production of let-7 miRNA.
  • This inhibition effectively removes an antitumorigenic miRNA, facilitating cancer progression.

Conclusions:

  • Cancer cells appropriate the Lin-28-mediated inhibition of let-7 biogenesis, a key developmental pathway.
  • This hijacking allows cancer cells to evade the tumor-suppressive effects of let-7 miRNA.
  • Targeting this regulatory axis may offer novel therapeutic strategies for cancer treatment.

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