Long non-coding RNAs (lncRNAs) with more than 200 nuleotides, have been explored to participate in various cancer types including osteosarcoma (OS), which is the most common kind of primary bone tumors with high morbidity in infants and adolescents. These oncogenic or tumor suppressive lncRNAs regulate OS pathogenesis, such as cell growth, proliferation, invasion, migration, metastasis and cell apoptosis, serve as independent prognostic biomarkers or play a significant role in multidrug resistance (MDR) in OS cells. In this review, we attempt to dissect the participation of lncRNAs in pathogenesis of OS and their potential clinical values, and also provide an outlook for viable biomarkers and therapeutic targets in OS.
ObjectiveMultiple clinical similarities exist between IgG4-related sclerosing cholangitis (IgG4-SC) and primary sclerosing cholangitis (PSC), and while gut dysbiosis has been extensively studied in PSC, the role of the gut microbiota in IgG4-SC remains unknown. Herein, we aimed to evaluate alterations of the gut microbiome and metabolome in IgG4-SC and PSC.DesignWe performed 16S rRNA gene amplicon sequencing of faecal samples from 135 subjects with IgG4-SC (n=34), PSC (n=37) and healthy controls (n=64). A subset of the samples (31 IgG4-SC, 37 PSC and 45 controls) also underwent untargeted metabolomic profiling.ResultsCompared with controls, reduced alpha-diversity and shifted microbial community were observed in IgG4-SC and PSC. These changes were accompanied by differences in stool metabolomes. Importantly, despite some common variations in the microbiota composition and metabolic activity, integrative analyses identified distinct host–microbe associations in IgG4-SC and PSC. The disease-associated genera and metabolites tended to associate with the transaminases in IgG4-SC. Notable depletion of Blautia and elevated succinic acid may underlie hepatic inflammation in IgG4-SC. In comparison, potential links between the microbial or metabolic signatures and cholestatic parameters were detected in PSC. Particularly, concordant decrease of Eubacterium and microbiota-derived metabolites, including secondary bile acids, implicated novel host–microbial metabolic pathways involving cholestasis of PSC. Interestingly, the predictive models based on metabolites were more effective in discriminating disease status than those based on microbes.ConclusionsOur data reveal that IgG4-SC and PSC possess divergent host–microbe interplays that may be involved in disease pathogenesis. These data emphasise the uniqueness of IgG4-SC.
During tumorigenesis and development, participation of the tumor microenvironment is not negligible. As an important component in the tumor microenvironment, mesenchymal stem cells (MSCs) have been corroborated to mediate proliferation, metastasis, and drug resistance in many cancers, including osteosarcoma. What’s more, because of tumor site tropism, MSCs can be engineered to be loaded with therapeutic agents so that drugs can be precisely delivered to tumor lesions. In this review, we mainly discuss recent advances concerning the functions of MSCs in osteosarcoma and their possible clinical applications in the future.
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