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. 2007 Feb 15;67(4):1424-9.
doi: 10.1158/0008-5472.CAN-06-4218.

Genetic unmasking of an epigenetically silenced microRNA in human cancer cells

Amaia Lujambio  1 , Santiago Ropero, Esteban Ballestar, Mario F Fraga, Celia Cerrato, Fernando Setién, Sara Casado, Ana Suarez-Gauthier, Montserrat Sanchez-Cespedes, Anna Git, Inmaculada Spiteri, Partha P Das, Carlos Caldas, Eric Miska, Manel Esteller
Affiliations

Genetic unmasking of an epigenetically silenced microRNA in human cancer cells

Amaia Lujambio et al. Cancer Res. .

Erratum in

  • Cancer Res. 2007 Apr 1;67(7):3492. Gitt, Anna [corrected to Git, Anna]

Abstract

The mechanisms underlying microRNA (miRNA) disruption in human disease are poorly understood. In cancer cells, the transcriptional silencing of tumor suppressor genes by CpG island promoter hypermethylation has emerged as a common hallmark. We wondered if the same epigenetic disruption can "hit" miRNAs in transformed cells. To address this issue, we have used cancer cells genetically deficient for the DNA methyltransferase enzymes in combination with a miRNA expression profiling. We have observed that DNA hypomethylation induces a release of miRNA silencing in cancer cells. One of the main targets is miRNA-124a, which undergoes transcriptional inactivation by CpG island hypermethylation in human tumors from different cell types. Interestingly, we functionally link the epigenetic loss of miRNA-124a with the activation of cyclin D kinase 6, a bona fide oncogenic factor, and the phosphorylation of the retinoblastoma, a tumor suppressor gene.

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