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Published on: August 23, 2019

Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer

Dmitri Lodygin1, Valery Tarasov, Alexey Epanchintsev

  • 1Molecular Oncology, Max-Planck-Institute of Biochemistry, Martinsried, Germany.

Cell Cycle (Georgetown, Tex.)
|August 23, 2008
PubMed

Insights

MicroRNA miR-34a, a tumor suppressor, is silenced in many cancers by promoter CpG methylation. Reactivating miR-34a induces cell cycle arrest and senescence, highlighting its role in cancer development.

Area of Science:

  • Molecular Biology
  • Genetics
  • Oncology

Background:

  • The microRNA miR-34a is a known target of the tumor suppressor gene p53.
  • miR-34a can induce cell cycle arrest, senescence, and apoptosis when ectopically expressed.

Purpose of the Study:

  • To investigate the role of miR-34a in various cancers.
  • To determine if aberrant CpG methylation silences miR-34a expression in tumors.

Main Methods:

  • Analysis of miR-34a promoter methylation in primary tumors and cell lines using CpG methylation assays.
  • Quantification of miR-34a expression levels.
  • Assessment of cell cycle arrest, senescence, and apoptosis upon miR-34a re-expression.
  • Identification of miR-34a targets, such as CDK6.

Main Results:

  • miR-34a expression is frequently silenced in prostate cancer (79.1%) due to CpG methylation of its promoter.
  • CpG methylation and silencing of miR-34a were also observed in breast, lung, colon, kidney, bladder, pancreatic, and melanoma cancers.
  • Silencing of miR-34a was found to be dominant over p53-mediated transactivation.
  • Re-expression of miR-34a in cancer cell lines induced senescence and cell cycle arrest, partly via targeting CDK6.

Conclusions:

  • miR-34a functions as a tumor suppressor gene.
  • Inactivation of miR-34a through CpG methylation and transcriptional silencing is a common event in a wide spectrum of human cancers.

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