Hepsin Promotes Epithelial–Mesenchymal Transition and Cell Invasion Through the miR-222/PPP2R2A/AKT Axis in Prostate Cancer

PURPOSE: To determine the role and underlying mechanism of hepsin in epithelial–mesenchymal transition (EMT) and cell invasion in prostate cancer. METHODS: The expression of hepsin in prostate cancer tissue samples and cell lines was measured by immunohistochemical staining and Western blotting. The EMT and cell invasion abilities of prostate cancer cells were detected by Western blot and transwell assays. RNA transfection was used to inhibit or overexpress related genes. The expression of miR-222 was detected by RT-qPCR. A dual‑luciferase reporter gene assay was performed to determine the target of miR-222. RESULTS: Hepsin expression was upregulated in prostate cancer tissue samples and cell lines. Inhibition of hepsin attenuated EMT and cell invasion and downregulated the expression of miR-222. Decreased miR-222 expression enhanced the level of PPP2R2A, which in turn attenuated the AKT signaling. Activation of miR-222 or AKT could block the inhibitory effects on EMT and cell invasion induced by hepsin deficiency. CONCLUSION: Hepsin promotes EMT and cell invasion through the miR-222/PPP2R2A/AKT axis in prostate cancer.