Combining microRNA (miRNA) microarray assay, functional characterization, mechanistic studies with clinical validation, a team led by researchers from Southern Medical University identified FBX8 as a CRC metastasis suppressor downstream of miR-223, a metastasis promoting miRNA that is transcriptionally regulated by Myocyte enhancer factor (MEF2A). mTOR is a substrate of FBX8 for ubiquitin-mediated degradation and is required for FBX8 induced cell proliferation and invasion in CRC cells. FBX8 is down-regulated in human CRC tissues and correlates with MEF2A, miR-223 and mTOR expression levels. Notably, low FBX8 expression status in CRC tissues was a significant prognostic factor for poor overall survival of patients.
These findings illustrate FBX8 as a metastasis suppressor that functions through mTOR signaling pathway and has significant prognostic power.