Assaying microRNA loss-of-function phenotypes in mammalian cells Emerging tools and their potential therapeutic utility

MicroRNAs are small, non-coding RNAs that are increasingly appreciated to play critical roles in the modulation of gene expression. In mammalian cells, our knowledge regarding the full impact of microRNAs on cellular behavior remains fragmentary. This has been due, in significant part, to the limited availability of experimental tools for studying microRNA loss-of-function phenotypes. Recently, several strategies for achieving this goal have been developed. Here, we discuss these methodologies for inhibiting specific microRNAs in mammalian cells both in vitro and in vivo, compare and contrast the strengths and weaknesses of these approaches, and speculate regarding the future impact of these antagonists on the treatment of human diseases such as cancer. These emerging techniques enable the attenuation of microRNA function in a manner that is quite sequence-specific, relatively long-lasting and increasingly cost-effective. As such, some of these advances hold great promise in terms of their eventual utility as therapeutic agents.