Molecular Pathways Molecular Pathways: MicroRNAs as Cancer Therapeutics

MicroRNAs (miRNA) are approximately 18 to 25 nucleotides in length and affect gene expression by silencing the translation of messenger RNAs. Because each miRNA regulates the expression of hundreds of different genes, miRNAs can function as master coordinators, efficiently regulating and coordinating multiple cellular pathways and processes. By coordinating the expression of multiple genes, miRNAs are responsible for fine-tuning the cell’smost important processes, like the ones involved in cellular growth and proliferation. Dysregulation of miRNAs appears to play a fundamental role in the onset, progression and dissemination of many cancers, and replacement of downregulated miRNAs in tumor cells results in a positive therapeutic response. Thus, in theory, inhibition of a particular miRNA linked to cancer onset or progression can remove the inhibition of the translation of a therapeutic protein—and conversely, administration of a miRNA mimetic can boost the endogenous miRNA population repressing the translation of an oncogenic protein. Although several basic questions about their biologic principles still remain to be answered, and despite the fact that all data with respect to miRNAs and therapy are still at the preclinical level, many specific characteristics of miRNAs in combination with compelling therapeutic efficacy data have triggered the research community to start exploring the possibilities of using miRNAs as potential therapeutic candidates. Clin Cancer Res; 18(16); 4234–9. 2012 AACR.