ABSTRACT: The chromosome 8q21 locus, which contains NKX3.1 and microRNA (miR)-3622 family (miR-3622a/b), is a frequently deleted region in human prostate cancer. Thus, miR-3622 is proposed as a tumor suppressor in various cancers, including prostate cancer, but its role remains debatable. In the present study, we found that mature miR-3622b-3p expression was higher in human prostate cancer than in normal prostate, while expression of miR-3622a was downregulated in human prostate cancer. Also, miR-3622b-3p facelifted cell proliferation, migration and invasion, whereas miR-3622a-3p inhibited cell migration and invasion but not proliferation in human prostate cancer cells. To address the role of miR-3622 locus, we knockout (KO) endogenous miR-3622, including both miR-3622a/b, in various human prostate cancer cell lines. Our data showed that miR-3622 KO reduced cell proliferation, migration, and invasion in vitro and tumor growth and metastasis in vivo. Functional analysis revealed that miR-3622 regulated p53 downstream gene network, including p21, c-MYC, and AIFM2, to control the cell cycle and apoptosis. Furthermore, using CRISPR interference, miRNA/mRNA immunoprecipitation assay, and dual-luciferase assay, we identified AIFM2, a direct target gene of miR-3622b-3p, that is responsible for miR-3622 KO-induced apoptosis. Also, we established a miR-3622-AIFM2 axis that contributes to oncogenic function during tumor progression. In addition, miR-3622 KO inhibited the epithelial-mesenchymal transition via upregulation of vimentin involved in prostate cancer metastasis. Our results suggest that miR-3622b-3p is overexpressed in human prostate cancer and plays an oncogenic role in tumor progression and metastasis via repression of p53 signaling, especially through a miR-3622-AIFM2 axis. On the other hand, deletion of miR-3622 at 8q21 locus in human prostate cancer may reduce oncogenic effects on tumor progression and metastasis.
