TYMSOS-miR-101-3p-NETO2 axis promotes osteosarcoma progression.

Background: Osteosarcoma (OS) is a type of bone cancer most often affects pre-teens and teens, but it is still a rare disorder. Neuropilin and tolloid-like 2 (NETO2) has been reported to promote OS progression, but its upstream mechanism in OS cells remains obscure.

Methods: Quantitative real-time PCR (RT-qPCR) and Western blot were conducted to examine RNA and protein levels, separately. Functional assays were performed to assess the impact of NETO2 on OS cell malignancy. Moreover, bioinformatics analyses and mechanism experiments were performed to identify the upstream mechanism of NETO2 in OS cells.

Results: Functionally, NETO2 depletion repressed cell proliferation, migration and invasion as well as epithelial-mesenchymal transition (EMT) but triggered the apoptosis of OS cells. NETO2 is directly targeted and negatively regulated by microRNA-101-3p (miR-101-3p). Mechanically, miR-101-3p could combine with long noncoding RNA (lncRNA) TYMS opposite strand RNA (TYMSOS) in OS cells. In addition, our study proved that TYMSOS promotes the malignancy of OS via elevating NETO2 expression as miR-101-3p sponge.

Conclusion: TYMSOS-miR-101-3p-NETO2 axis promotes the malignant behaviors of OS cells, which might offer a novel sight for OS treatment.