MiR-214 suppressed ovarian cancer and negatively regulated semaphorin 4D.

Ovarian cancer is one of the most common human malignancies in women. MiR-214 and semaphorin 4D (sema 4D) were found to be abhorrently expressed and involved in the progress of several kinds of malignant cancers. This study is aimed to investigate the cellular role of miR-214 and demonstrate that miR-214 negatively regulated sema 4D in ovarian cancer cells. The data showed that miR-214 expression was consistently lower in ovarian cancer tissues and cells than those in the normal controls. Over-expression of miR-214 in ovarian cancer SKOV-3 cells inhibited cell proliferation and induced apoptosis. It was suggested that miR-214 functioned as the tumor suppressor in ovarian cancer. Bioinformatic analysis indicated that miR-214 possibly regulated sema 4D by binding the sema 4D messenger RNA (mRNA) 3'-untranslated region (UTR). Sema 4D mRNA and protein levels were up-regulated in ovarian cancer tissues and SKOV-3 cells. Up-regulation of miR-214 in SKOV-3 cell line suppressed the sema 4D expression in both protein and nucleic acid levels. While, down-regulation of miR-214 in SKOV-3 cells would increase sema 4D protein and nucleic acid expression levels. The effects of miR-214 up- and down-regulation on luciferase activities of wild-type (WT) sema 4D 3'-UTR were completely removed upon introduction of mutation in 3'-UTR of WT sema 4D. Therefore, the data also demonstrated that sema 4D was the direct target of miR-214 and was negatively regulated by miR-214 in ovarian cancer cells.