The microRNA Lifecycle in Health and Cancer

SIMPLE SUMMARY: MicroRNAs (miRNAs) regulate messenger RNA (mRNA) expression at the post-transcriptional level. They play an important role within physiological and pathological cellular processes by regulating an estimated 60% of all protein-coding genes. miRNAs are produced quickly through canonical or non-canonical pathways involving many steps and proteins. In cancer, these steps can be altered to promote tumour formation and progression. These aberrations can occur at the gene level, or can be induced during processing and regulation of the target mRNA. This review provides an overview of the current knowledge on the lifecycle of miRNAs in health and cancer. Understanding miRNA function and regulation is essential prior to potential future application of miRNAs as cancer biomarkers. ABSTRACT: MicroRNAs (miRNAs) are small non-coding RNAs of ~22 nucleotides that regulate gene expression at the post-transcriptional level. They can bind to around 60% of all protein-coding genes with an average of 200 targets per miRNA, indicating their important function within physiological and pathological cellular processes. miRNAs can be quickly produced in high amounts through canonical and non-canonical pathways that involve a multitude of steps and proteins. In cancer, miRNA biogenesis, availability and regulation of target expression can be altered to promote tumour progression. This can be due to genetic causes, such as single nucleotide polymorphisms, epigenetic changes, differences in host gene expression, or chromosomal remodelling. Alternatively, post-transcriptional changes in miRNA stability, and defective or absent components and mediators of the miRNA-induced silencing complex can lead to altered miRNA function. This review provides an overview of the current knowledge on the lifecycle of miRNAs in health and cancer. Understanding miRNA function and regulation is fundamental prior to potential future application of miRNAs as cancer biomarkers.