Abstract: Objective To investigate the mechanism of miR-495-3p / Wnt inhibitor factor 1 (WIF1) / Wnt signaling pathway in regulating the proliferation, migration and invasion of retinoblastoma (RB) cells. Methods The relationship between differential expression of WIF1 in RB patients and the clinically adverse phenotypes was analyzed by bioinformatics. The miRNAs which bind with WIF1 were predicted and verified by dual-luciferase reporter assay. RB cells with stable overexpression of WIF1 or miR-495-3p were constructed respectively. The expressions of WIF1 protein and Wnt pathway related proteins were detected by Western blotting. In vitro assays for cell proliferation, apoptosis, migration and invasion were conducted. The volume and weight of tumors were measured in nude mice transplanted with xenograft tumors. The expression level of WIF1 in RB tissues was analyzed by immunohistochemistry. Results WIF1 was lowly expressed in RB tissues, and the low expression of WIF1 was related to migration and invasion. WIF1 was the target of miR495-3p, which was verified by dual-luciferase reporter assay. Overexpression of WIF1 could inhibit cell proliferation, migration and invasion, affect cell cycle, and induce apoptosis. In vivo assay showed that the overexpression of WIF1 in RB tissues could inhibit tumor growth. The expression levels of β-catenin and c-Myc proteins were downregulated after WIF1 was overexpressed (P< 0. 05). Overexpression of miR-495-3p could reduce the expression level of WIF1 protein, increase the expression levels of β-catenin and c-My, promote cell proliferation, migration and invasion, and inhibit apoptosis (P< 0. 05). The increased expression of WIF1 could reverse the effect of miR-495- 3p on proliferation, migration, invasion and apoptosis of RB cells (P< 0. 05). Conclusion miR495-3p could inhibit proliferation, migration and invasion of RB cells, and induce apoptosis by WIF1 / Wnt signaling pathway.

Key words: retinoblastoma, miR-495-3p, signaling pathway