Original Article MicroRNA-122 targets delta-catenin to suppress the tumorigenic potential of prostate cancer cells

delta-Catenin is expressed abundantly in various human cancers, including prostate, brain, breast, and lung carcinomas, and is recognized as an oncogene that promotes cancer cell growth and tumorigenesis. Although sev-eral transcriptional and post-translational pathways for delta-catenin regulation have been identified in cancer cells, the potential effects of microRNA-mediated regulation remain elusive. Here, we used a delta-catenin 3'-UTR luciferase re-porter assay to identify regulatory microRNAs. Subsequent bioinformatics analyses and molecular studies revealed that overexpression of miR-122 downregulated delta-catenin expression significantly via targeted binding to a seed se-quence in the 3'-UTR region of delta-catenin, and suppressed the invasion, migration, and proliferation of prostate can-cer cells in vitro. In a TRAMP-C2 mouse syngeneic prostate tumor model, stable expression of miR-122 decreased both delta-catenin expression and tumor growth. Mechanistically, overexpression of miR-122 inhibited the expression of delta-catenin-mediated downstream factors significantly in prostate cancer cells, including c-myc and cyclin D1. In cells overexpressing miR-122, there was no additive or synergistic effect of siRNA-mediated knockdown of delta-catenin on cell invasiveness, and overexpression of miR-122 alone had a more pronounced suppressive effect on cell invasion than knockdown of delta-catenin alone. These results suggest that miR-122 acts as tumor suppressor in prostate can-cer, mainly by downregulating delta-catenin expression, but also by targeting other factors. Indeed, subsequent experi-ments showed that overexpression of miR-122 reduced the levels of the mRNAs encoding myc, snail, and VEGF in prostate cancer cells. Overall, our findings demonstrate that targeting of delta-catenin by miR-122 represses the motility and tumorigenesis of prostate cancer cells, indicating a tumor suppressive effect of this miRNA in prostate cancer.