Small molecules with big roles in microRNA chemical biology and microRNA-targeted therapeutics

ABSTRACTMicroRNAs (miRNAs) are small, non-coding RNAs that post-transcriptionally regulate gene expression. Aberrant miRNA expression or function have close links with various human diseases. Therefore, therapeutic treatments with disease-associated miRNAs as targets are emerging. However, the intracellular miRNA networks are extremely complicated and poorly understood, which thus hinder the development of miRNA-targeted therapeutics. Small molecules that are able to regulate endogenous miRNAs hold great potential in both elucidation of miRNA networks and treatment of miRNA-related diseases. Herein, we summarize current strategies for discovery of small molecule modifiers of miRNAs, and we highlight aspects of miRNA cellular biology elucidated by using these small molecules and miRNA-targeted therapeutics realized by these small molecules. We envision that this area will expand dramatically in the near future and will ultimately contribute to a better understanding of miRNA-involved cellular processes and development of therapeutic agents for miRNA-associated diseases.