Hsa_circ_0093741 competes with FRS2 for miR-562 binding sites to promote nephroblastoma progression

Background: Circular RNA (circRNA) has been shown to play an essential role in cancer progression, including nephroblastoma. Hsa_circ_0093741 was discovered to be highly expressed in nephroblastoma. However, its function and mechanism in nephroblastoma development are still vague.

Methods: The expression levels of hsa_circ_0093741, miR-562 and FRS2 (Fibroblast Growth Factor Receptor Substrate 2) were detected using western blotting and quantitative real-time polymerase chain reaction. Functional experiments were performed by using cell counting kit-8, colony formation, 5-ethynyl-2'-deoxyuridine (EdU), transwell, scratch assays in vitro and animal experiments in vivo. The interaction analysis was conducted using dual-luciferase reporter assay and RIP assay.

Results: Hsa_circ_0093741 was highly expressed in nephroblastoma tissues and cells. Functionally, hsa_circ_0093741 silencing significantly suppressed the growth, invasion, and migration of nephroblastoma cells in vitro. MiR-562 was decreased in nephroblastoma, and was validated to be a target of hsa_circ_0093741. Inhibition of miR-562 reversed the anticancer functions of hsa_circ_0093741 silencing on nephroblastoma cells. FRS2 expression was increased in nephroblastoma and served as a target of miR-562, moreover, FRS2 overexpression attenuated the inhibitory functions of miR-562 on the nephroblastoma cell malignant phenotypes mentioned above. Pre-clinically, lentivirus-mediated hsa_circ_0093741 silencing also impeded nephroblastoma tumor growth and metastasis in vivo.

Conclusion: Knockdown of hsa_circ_0093741 suppresses nephroblastoma cell growth, migration and invasion by regulating the miR-562/FRS2 axis, suggesting the potential involvement of hsa_circ_0093741 in nephroblastoma progression.