Expression, Activation and Pre-Clinical Relevance of Exosome-Transmitted Circular RNA hsa_circ_0000190 in Osteosarcoma Progression

Abstract

Background: Under the microenvironment, tumor progression is substantially affected by cell-cell communication. In spite of the mediating effect of exosomes on cell-cell communication by packaging into circRNAs, the effect of exosomal circRNA hsa_circ_0000190 (circ-0000190) in osteosarcoma is still not clear. Methods: Circ-0000190 expressions in tissues and exosomes from plasma were compared between osteosarcoma patients and controls. Thereafter ROC and AUC were applied to examine whether the diagnostic results were accurate, and the effect of exosomal circ-0000190 was dug out via the determination of cell phenotypes and animal assays. Results: Results showed circ-0000190 exhibited an obvious reduction in exosomes and tissues of osteosarcoma patients (P<0.05). It was also discovered that exosomes encapsulated the majority of circ-0000190, and exosome-encapsulated circ-0000190 could be applied to make a distinction between osteosarcoma patients and controls (AUC = 0.9006). Besides, exosomal circ-0000190 in osteosarcoma cells transported from normal cells weakened the capacities of osteosarcoma cells to migrate, proliferate and invade, so as to block their biological malignant behaviors (P<0.05). In addition, under the action of exosomal circ-0000190, tumor growth was impeded and the expression of TET1 was inhibited via the competitive binding to miR-767-5p. Conclusion: In all, exosomal circ-0000190 has a good prospect as it can be regarded as a new biomarker for detecting osteosarcoma. Exosomal circ-0000190 transported from normal cells to osteosarcoma cells impeded the in-vitro and in-vivo development of osteosarcoma, implying that exosomal circ-0000190 exerts an effect on communication between normal cells and osteosarcoma cells in the carcinogenesis process of osteosarcoma. Funding Statement: The authors state: None. Declaration of Interests: All of the contributors in this study declared no conflict of interest. Ethics Approval Statement: The research was approved by the Ethics Committee of Cancer Hospital of China Medical University. Animal assays were approved by the Institutional Animal Care and Use Committee of Cancer Hospital of China Medical University.