Micro-orchestrating differentiation in cancer

Differentiation involves repression of genes governing proliferation and self-renewal, and transcriptional activation of lineage-specific genes. The mechanisms underlying these changes are epigenetic. In cancer cells differentiation genes are locked into a transcriptionally inactive state. Recent results show that in spite of the diversity of the genetic lesions leading to a cancerous phenotype, it may still be possible to release this block and to force differentiation. The key may be microRNAs (miRNAs) which directly or indirectly target epigenetic modifiers. These miRNAs could allow the non-toxic differentiative approach currently adopted in some hematologic malignancies to apply to solid tumors.