BackgroundThere 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.MethodsThe 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.ResultsIn 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 of cell proliferation, migration, and invasion, which was induced by circFAT1 knockdown, and therefore promoted tumorigenesis.ConclusionsOur findings demonstrate a novel function of circFAT1 in tumorigenesis and suggest a new therapeutic target for the treatment of osteosarcoma.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0917-7) contains supplementary material, which is available to authorized users.

Herein, we have developed a simple and facile method to synthesize yolk-shell nanostructured FeO@C nanoparticles (NPs) as a multifunctional biosensing platform for the label-free colorimetric detection of HO and glucose. It was demonstrated that FeO@C yolk-shell nanostructures (YSNs) retained the magnetic properties that can be used for separation and concentration. Also importantly, the FeO@C YSNs exhibited an intrinsic peroxidase-like activity that could quickly catalyze the enzyme substrate in the presence of HO and produce a blue color. Compared to other similar ferric oxide-based NPs with different structures, FeO@C YSNs exhibited greatly enhanced catalytic activities due to their unique structural features. Moreover, steady-state kinetics indicated the catalytic behaviors in agreement with the classic Michaelis-Menten models. Taking advantage of the high catalytic activity, FeO@C YSNs were employed as novel peroxidase mimetics for label-free, rapid, sensitive, and specific colorimetric sensing of HO and glucose, suggesting that FeO@C YSNs have the potential for construction of portable sensors in the application of point-of-care (POC) diagnosis and on-site tests.

Because of the short size and low abundance of microRNAs, it is challenging to develop fast, inexpensive, and simple biosensors to detect them. In this work, we have demonstrated a new generation (the third generation) of E-DNA sensor for the sensitive and specific detection of microRNAs. Our third generation of E-DNA sensor can sensitively detect microRNA target (microRNA-141) as low as 1 fM. The excellent specificity has been demonstrated by its differential ability to the highly similar microRNA analogues. In our design, the use of DNA tetrahedron ensures the stem-loop structure in well controlled density with improved reactivity. The regulation of the thermodynamic stability of the stem-loop structure decreases the background signal and increases the specificity as well. The enzymes attached bring the electrocatalytic signal to amplify the detection. The combination of these effects improves the sensitivity of the E-DNA sensor and makes it suitable to the microRNA detection. Finally, our third generation of E-DNA sensor is generalizable to the detection of other micro RNA targets (for example, microRNA-21).

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