miR-484 is associated with disease recurrence and promotes migration in prostate cancer.

BACKGROUND:microRNAs (miRs) regulate the expression of protein-coding genes and play key roles in various biological processes, including development and immunity. However, dysregulation of miR expression is also involved in disease biology, including cancer. METHODS:We utilized The Cancer Genome Atlas (TCGA) and other publicly available databases for miRs and mRNA expression in prostate cancer, selected miR-484 and investigated its role in prostate cancer biology and disease progression using in vitro studies. RESULTS:Our data mining efforts revealed that increased miR-484 in prostate tumors associates with early disease recurrence, while miR-484 expression in human prostate cancer cells enhances cancer cell mobility. Using RNAseq and bioinformatics, we identified candidate target genes of miR-484 and generated a list of potential tumor suppressors. One candidate in this list was PSMG1. We applied luciferase assays and immunoblotting to confirm that miR-484 directly targets PSMG1. Additional in vitro assays with cancer cell lines showed that PSMG1 knockdown rescued the reduction in mobility brought on by miR-484 inhibition, pointing toward the existence of a miR-484-PSMG1 axis in prostate cancer. CONCLUSIONS:We hypothesize that miR-484 is an oncogene in the prostate that increases cancer cell mobility, with PSMG1 being a mir-484 target in this process.

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