Hsa_circ_0088212-mediated MiR-520 h/APOA1 Axis Inhibits Osteosarcoma Progression

Background: It has been known for decades that circRNAs are deregulated in cancer. Here, we characterized the role and underlying mechanism of circ_0088212 in osteosarcoma.

Methods: The expression levels of circ_0088212, miR-520 h, and APOA1 were determined by RT-qPCR. RNase R digestion was performed to verify the circular structure of circ_0088212. CCK8 and transwell invasion assays were conducted to examine the in vitro malignancy of osteosarcoma. Caspase-3 activity was also measured. An in vivo model of osteosarcoma was constructed to examine the in vivo effect of circ_0088212 on osteosarcoma. Luciferase reporter, RNA RIP, and RNA pull-down assays were performed to verify the interaction between miR-520 h and APOA1 or circ_0088212.

Results: Circ_0088212 and APOA1 were expressed at low levels in osteosarcoma tissues and cells, while miR-520 h was highly expressed. Overexpression of circ_0088212 was found to inhibit the in vitro and in vivo growth of osteosarcoma. Mechanistically, miR-520 h was the target of circ_0088212 and APOA1 was the target of miR-520 h. Circ_0088212 downregulated miR-520 h expression, while miR-520 h overexpression abolished the inhibitory effect of circ_0088212 on osteosarcoma cell proliferation and migration. Furthermore, miR-520 h overexpression led to reduced APOA1 expression, while APOA1 overexpression counteracted the oncogenic effect of miR-520 h in osteosarcoma cells.

Conclusion: Our findings demonstrated that circ_0088212 might exert a tumor-suppressive activity in osteosarcoma by sponging and sequestering miR-520 h away from APOA1. This suggests that the circ_0088212/miR-520 h/APOA1 axis may be a promising therapeutic target for osteosarcoma intervention.