Abstract: Objective:To investigate the role of miRNA-15a in the progression and metastasis of ovarian cancer and to explore the specific related molecular mechanism.Methods:Thirty-two ovarian cancer specimens were collected from the First Affiliated Hospital of Jinzhou Medical University from May 2012 to June 2015.MiRNA-15a expression in ovarian cancer tissues and corresponding adjacent tissues was detected by RT-PCR.SKOV-3 ovarian cancer cells were transfected with miRNA-15a mimics in the experimental group or control miRNA in the control group, and the effects of miRNA-15a on cell proliferation, invasion, and apoptosis were detected by CCK8, transwell, and flow cytometry assays, respectively.Expression levels of key proteins involved in related pathways were detected by Western blot.Candidate target genes of miRNA-15a were identified by bioinformatics screening and verified by dual luciferase reporter gene and Western blot assays.Wnt3a was co-transfected with miRNA-15a mimic into SKOV-3 cells to detect its effects on cell proliferation, invasion, and signaling.Results:Compared with that in adjacent tissues (0.911±0.209), miRNA-15a expression was significantly down-regulated in ovarian cancer tissues (0.692±0.228)(P < 0.05).Compared with that in the control group, cell proliferation in the experimental group was significantly lower (P < 0.05).Moreover, compared with that in the control group (189.667±14.742), invasive cells in the experimental group were fewer (96.667±13.614)(P < 0.05).Compared with that in the control group (6.933%±0.379%), the apoptotic rate in the experimental group was (27.400%±0.854%)(P < 0.05).Furthermore, miRNA-15a mimics down-regulated Wnt3a, β-catenin, cyclin D1, and vascular endothelial growth factor expression and up-regulated E-cad expression.Dual luciferase reporter gene assay and Western blot results indicated that miRNA-15a directly targets Wnt3a.Importantly, we found that up-regulation of Wnt3a significantly decreased the inhibitory effect of miRNA-15a on the proliferation, invasion, and Wnt/β-catenin signaling pathway in SKOV 3 cells. Conclusions: MiRNA-15a could inhibit ovarian cancer progression and metastasis by directly targeting Wnt3a and regulating the Wnt/β-catenin pathway.