Extracellular nanovesicles‐transmitted circular RNA has_circ_0000190 suppresses osteosarcoma progression

Abstract

Under the microenvironment, tumour progression is substantially affected by cellcell communication. In spite of the mediating effect of extracellular nanovesicles (EVs) on cell-cell communication by packaging into circRNAs, the effect of EVs circRNA hsa_circ_0000190 (circ-0000190) in osteosarcoma is still not clear. Circ-0000190 expressions in tissues and EVs from plasma were compared between osteosarcoma patients and controls. Thereafter, receiver operating characteristic (ROC) curve was drawn and area under the curve was calculated to examine whether the diagnostic results were accurate, and the effect of EVs circ-0000190 was dug out via the determination of cell phenotypes and animal assays. Results showed circ-0000190 exhibited an obvious reduction in EVs and tissues of osteosarcoma patients (P < .05). It was also discovered that EVs encapsulated the majority of circ-0000190, and EVs-encapsulated circ-0000190 could be applied to make a distinction between osteosarcoma patients and controls. Besides, EVs 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 behaviours (P < .05). In addition, under the action of EVs circ-0000190, tumour growth was impeded and the expression of TET1 was inhibited via the competitive binding to miR-767-5p. In all, EVs circ-0000190 has a good prospect as it can be regarded as a new biomarker for detecting osteosarcoma. EVs circ-0000190 transported from normal cells to osteosarcoma cells impeded the in vitro and in vivo development of osteosarcoma, implying that EVs circ-0000190 exerts an effect on communication between normal cells and osteosarcoma cells in the carcinogenesis process of osteosarcoma.

Diagnostic and Prognostic Significance of Dysregulated Expression of Circular RNAs in Osteosarcoma

“…Moreover, 22 studies were further eliminated with a variety of reasons, including ve studies not related to circRNAs or osteosarcoma, six studies did not report outcomes, two reviews and case reports, four animal studies, and ve lack of extractable data. Finally, 26 studies comprising 1,652 osteosarcoma cases were enrolled in this quantitative study, with 18 on clinicopathological features, ten on diagnosis [13,18,19,21,24,[30][31][32][33][34] [12,14,18,19,[32][33][34][36][37][38][39][40], whereas other two studies on downregulated circRNAs applying ≥ 18 or < 18 years old to separate enrolled patients [13,30]. In consideration of the consistency, only these studies with common cut-off value were included in the following meta-analysis with regard to patients' age.…”

“…CircRNAs were regarded as oncogenes or tumor-suppressor in terms of their expression levels. Speci cally, 21 circRNAs were identi ed as oncogenic circRNAs with upregulated expression pattern [12, 14, 16-23, 31-34, 36, 37, 39-43], while the other ve were recognized as tumor suppressors [13,24,30,35,38] with downregulated expression, respectively. The duration for follow-up ranged from 40 to 125.…”

“…The duration for follow-up ranged from 40 to 125. For diagnostic assay, ten studies with data on sensitivity, speci city and AUC [13,18,19,21,24,[30][31][32][33][34]. The quality of studies was evaluated by QUADAS II and NOS scores.…”

Diagnostic and prognostic significance of dysregulated expression of circular RNAs in osteosarcoma

“…The duration for follow-up ranged from 40 to 125. For diagnostic assay, ten studies with data on sensitivity, specificity and AUC (9,15,16,(22)(23)(24)(25)(26)(27)(28).…”

“…Finally, 26 studies comprising 1,652 osteosarcoma cases were enrolled in this quantitative study, with 18 on clinicopathological features, ten on diagnosis(9,15,16,(22)(23)(24)(25)(26)(27)(28) and 18 on prognosis(9, 10, 12-16, 22-25, 27, 29-40).…”