miR-938 Promotes the Proliferation and Invasion of Prostate Cancer Through Targeting Pleckstrin Homology (PH) Domain Leucine-Rich-Repeats Protein Phosphatase 2 and Forkhead Box O3

Abstract

miR-938 is generally reported to be up-regulated in various cancers, which affect the tumor progression. In the present study, we investigated the biological role and underlying mechanisms of miR-938 in prostate cancer (PCa). PCa is the most common malignant tumor in males with markedly increasing incidence in recent years. Up-regulation of miR-938 occurred in PCa tissues and cell lines at mRNA level. Functional assays were established to demonstrate that miR-938 mimics significantly promoted the proliferation, migration and invasion of PCa cells, while knockdown of miR-938 led to the inhibition. Luciferase activity assay suggested miR-938 directly bound to the 3 UTR of PHLPP2 (Pleckstrin Homology (PH) domain Leucine-rich-repeats Protein Phosphatase 2) and FOXO3 (Forkhead box O3). Our results also showed that the regulation activity of miR-938 on progression of PCa was partially through its negative regulation on PHLPP2 and FOXO3. Our results deciphered the mechanism through which miR-938 promoted the progression of PCa by activation of PI3K/AKT signal pathway. Together, inactivation of PI3K/AKT signal pathway through down-regulation of miR-938 could be an important mechanism in inhibiting PCa progression, thus shedding light on the development of novel anti-tumor therapies for treatment of PCa.