Retinoblastoma (RB) is an intraocular malignancy that occurs in children. Circular RNAs (circRNAs) have been confirmed to play an essential role in tumorigenesis and development. This study aimed to ascertain the role and potential mechanism of hsa_circ_0099198 in RB. The levels of circ_0099198, microRNA-1287 (miR-1287) and low-density lipoprotein receptor-related protein 6 (LRP6) were determined by real-time quantitative polymerase chain reaction and Western blot. Cell proliferation was assessed by colony formation assay. Cell cycle arrest and apoptosis were evaluated by flow cytometry. Cell migration and invasion were tested using transwell assay. The activity of caspase-3/caspase-9 was examined with commercial kits. The interaction among circ_0099198, miR-1287 and LRP6 were verified by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay or RNA pull-down assay. Xenograft experiment was used to assess tumor growth in vivo. circ_0099198 and LRP6 levels were increased, while miR-1287 level was reduced in RB cells. circ_0099198 silencing suppressed proliferation and metastasis and expedited cell cycle arrest and apoptosis in Y79 and So-RB50 cells. In addition, depletion of circ_0099198 inhibited RB cell progression via regulating miR-1287/LRP6 axis. Moreover, knockdown of circ_0099198 blocked the growth of xenograft tumors. circ_0099198 contributed to RB progression by sponging miR-1287 and up-regulating LRP6, which provided novel biomarkers for RB therapy.
Keywords: LRP6; Retinoblastoma; circ_0099198; miR-1287.
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