RNA-Directed Epigenomic Reprogramming-An Emerging Principle of a More Targeted Cancer Therapy?

Epigenetic aberrations are recognized as an early and common event during carcinogenesis. This provides a strong rationale for a therapeutic intervention at the epigenetic level. Current epigenetically active drugs, however, lack specificity for particular genomic loci. Better processes for a more targeted manipulation of the cancer epigenome are needed. One option could be the ability of long noncoding RNAs (lncRNAs) to recruit the chromatin modification complexes to particular genomic loci. In consequence, epigenetic variations would not be stochastic but controlled by a directed programme, through which specific groups of genes are regulated by promoter methylation and(or) histone marks, even if located on different chromosomes. lncRNAs are known to be functionally involved in cell fate specification and carcinogenesis. Depleting lncRNAs with oncogenic potential or replacing scarce molecules with tumor suppressor activity could therefore be employed for a specific reprogramming of the epigenome of cancer cells. Apart from the targeted manner and thus specificity, the mode of action by itself could be an advantage of lncRNA-associated therapy. Similar to what happens naturally during cell fate decisions, the whole developmental programme of a cell or particular parts of it could be reset. In consideration of the early onset of epigenetic aberrations, such an approach could even be useful for cancer prevention. (C) 2011 Wiley Periodicals, Inc.