The Lilliputians and the Giant: An Emerging Oncogenic microRNA Network that Suppresses the PTEN Tumor Suppressor In Vivo.

MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that function via transcript degradation or translational inhibition, depending on the degree of complementarity with their target transcripts. They often exhibit temporal, spatial and developmental-stage specific expression, and have been found to be frequently dysregulated in multiple human diseases including various cancers. Numerous experimental and bioinformatic approaches have identified miRNAs that control cancer initiation and progression by directly targeting key oncogenes or tumor suppressors. PTEN (phosphatase and tensin homolog deleted on chromosome 10) is one of the most frequently disrupted tumor suppressor genes in multiple human cancers. PTEN is particularly susceptible to miRNA regulation as subtle changes in its dose have been shown to have a profound effect on tumorigenesis in vivo. Here we will review emerging evidence describing a vast layer of miRNA-mediated PTEN regulation, with a specific focus on their function in animal models in vivo, therapeutic implications, and directions for future research.