CircFAT1 sponges miR-375 to promote the expression of Yes-associated protein 1 in osteosarcoma cells

作者：Gang Liu, Kangmao Huang, Zhiwei Jie, Yizheng Wu, Junxin Chen, Zizheng Chen, Xiangqian Fang, Shuying Shen · 发表于：Molecular Cancer · 年份：2018 · DOI：10.1186/s12943-018-0917-7 · 被引用次数：170 · 研究领域：Circular RNAs in diseases、Hippo pathway signaling and YAP/TAZ、Sarcoma Diagnosis and Treatment

BACKGROUND: There is an urgent need to identify new molecular targets for treatment of osteosarcoma. Circular RNAs are a class of endogenous RNAs that are extensively found in mammalian cells and exert critical functions in the regulation of gene expression, but in osteosarcoma the underlying molecular mechanism of circular RNAs remain poorly understood. Here we assessed the tumorigenesis properties of a circular RNA, circFAT1 in osteosarcoma. METHODS: The effects of circFAT1/miR-375/YAP1 was evaluated on human osteosarcoma cells growth, apoptosis, migration, invasion and tumorigenesis. Signaling pathways were analyzed by western blotting, qRT-PCR, fluorescence in situ hybridization, chromogenic in situ hybridization,RNA Binding Protein Immunoprecipitation and immunofluorescence. The consequence of circFAT1 short hairpin RNA combined or not with miR-375 sponge was evaluated in mice bearing 143B xenografts on tumor growth. RESULTS: In this study, we observed significant upregulation of circFAT1 originating from exon 2 of the FAT1 gene in human osteosarcoma tissues and cell lines. Inhibition of circFAT1 effectively prevented the migration, invasion, and tumorigenesis of osteosarcoma cells in vitro and repressed osteosarcoma growth in vivo. Mechanistic studies revealed that circFAT1 contains a binding site for the microRNA-375 (miR-375) and can abundantly sponge miR-375 to upregulate the expression of Yes-associated protein 1. Moreover, inhibition of miR-375 reversed attenuation...