Circular RNA (circRNA) is a key regulator in the development and progression of human cancers, however its role in osteosarcoma tumorigenesis is not well understood. The present study aims to investigate the expression profiles and potential modulation of circRNA on osteosarcoma carcinogenesis. Human circRNA microarray was performed to screen for abnormally expressed circRNA in osteosarcoma tissue and circRNA-0008717 was identified as one circRNA significantly upregulated in osteosarcoma tissue. Osteosarcoma patients with high circRNA-0008717 expression had shortened survival. Gain and loss functional assays suggested that knockdown of circRNA-0008717 suppressed cell proliferation, migration and invasion, but promoted cell apoptosis. By using biotin-labeled circRNA-0008717 probe to perform RNA precipitation in osteosarcoma cells, we identified miR-203 as the circ0008717-associated microRNA. Subsequently, Bmi-1 was identified as the functional target of miR-203. In addition, overexpression of circRNA-0008717 in osteosarcoma could elevate Bmi-1 expression, resulting in the promotion of osteosarcoma cell proliferation and invasion. Furthermore, the tumor promoting effect of circRNA-0008717 was abolished by miR-203 mimics or Bmi-1 silencing vector. In conclusion, circRNA-0008717 plays an oncogenic role in osteosarcoma and may serve as a promising prognostic biomarker for osteosarcoma patients. Therefore, silence of circRNA-0008717 could be a future direction to develop a novel treatment strategy.

Osteosarcoma (OS) is the major type of primary bone tumor and is associated with a poor prognosis due to chemotherapy resistance. Accumulating evidence indicates that microRNAs (miRNAs/miRs) may influence the tumor progression of OS and cell sensitivity to chemotherapy. In the present study, a total of 7 patients with OS and 7 healthy volunteers were recruited. Reverse transcription-quantitative polymerase chain reaction and ELISA were performed to determine the expression of miRNAs and mRNAs in the serum of participants. Furthermore, the biological function of miR-22 and S100A11 was examined in MG-63 cells using Cell Counting Kit-8 assays, Transwell migration assays and western blot analysis to determine the effects on cell proliferation, migration and protein expression, respectively, while MG-63 cell sensitivity to cisplatin was assessed by measuring cell viability following cisplatin treatment and calculating the half maximal inhibitory concentration (IC50). Additionally, the association between miR-22 and S100 calcium-binding protein A11 (S100A11) was validated using a luciferase reporter assay. The results demonstrated that miR-22 expression was significantly reduced in patients with OS and the MG-63 OS cell line, compared with healthy volunteers and the normal osteoblast hFOB 1.19 cell line, respectively, while the expression of S100A11 was negatively associated with miR-22 levels in the MG-63 cell line. Furthermore, overexpression of miR-22 inhibited the proliferation and migratory ability of MG-63 cells, and increased the sensitivity of MG-63 cells to cisplatin treatment; however, overexpression of S100A11 partially attenuated the alterations in proliferation, migratory ability and chemosensitivity that were induced by miR-22 overexpression. In addition, it was confirmed that S100A11 is a direct target gene of miR-22 in MG-63 cells. In conclusion, to the best of our knowledge, the present study is the first to demonstrate that miR-22 may be a promising therapeutic target and may have potential as part of a combination treatment alongside chemotherapeutic agents for OS.