MicroRNA-129-5p suppresses proliferation, migration and invasion of retinoblastoma cells through PI3K/AKT signaling pathway by targeting PAX6

Abstract

BackgroundRetinoblastoma (RB) is the most common primary intraocular malignancy in children. Accumulating evidences have clarified that microRNAs (miRNAs) modulated signaling molecules by acting as oncogenes or tumor-suppressor genes in RB. Thus, in our study, we aimed to investigate the function of miR-129-5p in RB cells through PI3K/AKT signaling pathway by targeting PAX6. Two RB cell lines, Y79 and WERI-Rb-1, were selected in our study, followed by transfection of miR-129-5p inhibitor or si-PAX6 to explore the regulatory role of miR-129-5p in RB cell proliferation, invasion and migration. Material and methodsDual-luciferase assay was used for the detection of targeting relationship between miR-129-5p and PAX6. Besides, western blot analysis was applied to detect expression of cell cycle-related factors (CDK2 and Cyclin E) and PI3K/AKT signaling pathway-related factors (p-AKT and AKT). Nude mice tumorigenesis experiment was used to evaluate the effect of miR-129a-5p on RB growth in vivo. ResultsmiR-129-5p was down-regulated in RB cell lines. miR-129-5p directly targeted the 3′-untranslated region of PAX6. Artificial down-regulation of miR-129-5p promoted cell proliferation, migration and invasion in RB cell lines Y79 and WERI-Rb-1, and promoted RB growth in vivo via PI3K/AKT signaling pathway, which could be reversed by transfection with silencing PAX6. ConclusionThis study provides evidences that RB progression was suppressed by overexpressed miR-129-5p via direct targeting of PAX6 through PI3K/AKT signaling pathway, which may provide a molecular basis for better treatment for RB.