Potential therapeutic applications of microRNAs in response to DNA damage in cancer stem cells.

Following genomic insults, inefficient DNA repair mechanisms may transform stem cell to cancer stem cells that have extensive self-renewal and aberrant differentiation properties rendering them highly resistant to chemotherapeutic and ionizing radiations and thus may cause tumor relapse in patients. Mature microRNAs (miRNAs), new class of modulators are single-stranded RNA molecules of 20-23 nucleotide (nt) length can form specific base interactions with the mRNAs of the genes and mediate the biological processes ranging from tumor development, maintenance of stem cell phenotype and stress responses. Due to differential functional interactions of miRNAs in cancer stem cells versus normal and differentiated cells, various miRNA therapeutic methods may provide a promising tool to address aberrant miRNA expression and specifically targeting cancer stem cells to cure cancer. Manipulating miRNAs activities by using either antagomirs for knock down the oncogenic properties of miRNAs or miRNA mimics to restore the tumor suppressor functions in order to correct their aberrant transcript levels that can regulate cellular response to damage by modulating apoptotic, cell cycle proliferation, DNA repair, invasion and differentiation functions, are also being examined. The current article also focuses some of the potential innovative strategies to overcome the major concerns for the clinical RNAi translation, the delivery and safety. Future studies should be aimed to establish multiple clinical trials with the novel gene delivery methods with high transfection efficiency, minimum toxicity and tumor targeted ability for miRNA based therapy.