Endogenous miRNAa: miRNA-Mediated Gene Upregulation

The phenomenon of RNA activation (RNAa) was initially discovered by Li and colleagues about a decade ago. Subsequently, gene activation by exogenously expressed small activating RNA has been demonstrated in different cellular contexts by a number of laboratories. Conceivably, endogenously expressed microRNAs may also utilize RNA activation as a cellular mechanism for gene regulation, which may be dysregulated in disease states such as cancer. RNA activation can be applied to gain-of-function studies and holds great promise for disease intervention. This chapter will discuss examples of promoter-targeting microRNAs discovered in recent years and their pathophysiological relevance. I will also briefly touch upon other novel classes of microRNAs with positive gene regulatory roles, including TATA-box-activating microRNAs and enhancer-associated microRNAs.