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. 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. 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 of cell proliferation, migration, and invasion, which was induced by circFAT1 knockdown, and therefore promoted tumorigenesis. Our findings demonstrate a novel function of circFAT1 in tumorigenesis and suggest a new therapeutic target for the treatment of osteosarcoma.

Objective: Osteoporosis is a common musculoskeletal disease. Fractures caused by osteoporosis place a huge burden on global healthcare. At present, the mechanism of metabolic-related etiological heterogeneity of osteoporosis has not been explored, and no research has been conducted to analyze the metabolic-related phenotype of osteoporosis. This study aimed to identify different types of osteoporosis metabolic correlates associated with underlying pathogenesis by machine learning.Methods: In this study, the gene expression profiles GSE56814 and GSE56815 of osteoporosis patients were downloaded from the GEO database, and unsupervised clustering analysis was used to identify osteoporosis metabolic gene subtypes and machine learning to screen osteoporosis metabolism-related characteristic genes. Meanwhile, multi-omics enrichment was performed using the online Proteomaps tool, and the results were validated using external datasets GSE35959 and GSE7429. Finally, the immune and stromal cell types of the signature genes were inferred by the xCell method.Results: Based on unsupervised cluster analysis, osteoporosis metabolic genotyping can be divided into three distinct subtypes: lipid and steroid metabolism subtypes, glycolysis-related subtypes, and polysaccharide subtypes. In addition, machine learning SVM identified 10 potentially metabolically related genes, GPR31, GATM, DDB2, ARMCX1, RPS6, BTBD3, ADAMTSL4, COQ6, B3GNT2, and CD9.Conclusion: Based on the clustering analysis of gene expression in patients with osteoporosis and machine learning, we identified different metabolism-related subtypes and characteristic genes of osteoporosis, which will help to provide new ideas for the metabolism-related pathogenesis of osteoporosis and provide a new direction for follow-up research.

Hypoxia is an indispensable factor for cancer progression and is closely associated with the Warburg effect. Circular RNAs (CircRNA) have garnered considerable attention in molecular malignancy therapy as they are potentially important modulators. However, the roles of circRNAs and hypoxia in osteosarcoma (OS) progression have not yet been elucidated. This study reveals the hypoxia-sensitive circRNA, Hsa_circ_0000566, that plays a crucial role in OS progression and energy metabolism under hypoxic stress. Hsa_circ_0000566 is regulated by hypoxia-inducible factor-1α (HIF-1α) and directly binds to it as well as to the Von Hippel-Lindau (VHL) E3 ubiquitin ligase protein. Consequentially, binding between VHL and HIF-1α is impeded. Furthermore, Hsa_circ_0000566 contributes to OS progression by binding to HIF-1α (while competing with VHL) and by confers protection against HIF-1α against VHL-mediated ubiquitin degradation. These findings demonstrate the existence of a positive feedback loop formed by HIF-1α and Hsa_circ_0000566 and the key role they play in OS glycolysis. Taken together, these data indicate the significance of Hsa_circ_0000566 in the Warburg effect and suggest that Hsa_circ_0000566 could be a potential therapeutic target to combat OS progression.

Total joint arthroplasty is associated with significant blood loss and often requires blood transfusion. However, allogeneic blood transfusion (ABT) may lead to severe problems, such as immunoreaction and infection. Postoperative autotransfusion, an alternative to ABT, is controversial. We conducted a meta-analysis to evaluate the ability of postoperative autotransfusion to reduce the need for ABT following total knee arthroplasty (TKA) and total hip arthroplasty (THA). Systematic literature searches for randomized controlled trials were performed using PubMed, Embase, and the Cochrane Library until February 2016. Relative risks (RRs) and weighted mean differences with 95% confidence intervals (CIs) were calculated using fixed-effect or random-effect models; we also evaluated publication bias and heterogeneity. Seventeen trials with a total of 2314 patients were included in the meta-analysis. The pooled RRs of ABT rate between autotransfusion and the regular drainage/no drainage groups for TKA and THA were 0.446 (95% CI = 0.287, 0.693; p < 0.001) and 0.757 (95% CI = 0.599, 0.958; p = 0.020), respectively. In the subgroup analysis performed in TKA patients according to control interventions, the pooled RRs were 0.377 (95% CI = 0.224, 0.634; p < 0.001) (compared with regular drainage) and 0.804 (95% CI = 0.453, 1.426, p = 0.456) (compared with no drainage). In the subgroup analysis performed for THA, the pooled RRs were 0.536 (95% CI = 0.379, 0.757, p < 0.001) (compared with regular drainage) and 1.020 (95% CI = 0.740, 1.405, p = 0.904) (compared with no drainage). Compared to regular drainage, autotransfusion reduces the need for ABT following TKA and THA. This reduction is not present when comparing autotransfusion to no drainage. However, the reliability of the meta-analytic results concerning TKA was limited by significant heterogeneity in methods among the included studies.