Exosome-Delivered Hsa_Circ_0000116 Facilitates Osteosarcoma Cell Malignancy via PI3K/Akt/mTOR and p38/MAPK Pathways.

Abstract

Exosome-delivered circular RNAs (circRNAs) are recognized as a key mechanism that regulates osteosarcoma (OS) progression. The purpose of this study is to discover the role of a novel circRNA hsa_circ_0000116 from exosomes in OS progression. Transmission electron microscopy, nanoparticle tracking analysis, and western blotting were used to identify the exosomes isolated from two OS cell lines (HOS and MG-63). After coculturing exosomes with OS cells and transfecting hsa_circ_0000116 knockdown vector into OS cells, cell function experiments, including cell counting kit-8, wound healing, and Transwell experiments, were performed to assess the change of OS cell malignant phenotype. In addition, the levels of PI3K/Akt/mTOR and p38/MAPK pathways-associated proteins were measured using western blotting. Exosomes with around 100 nm in diameter were successfully isolated from HOS and MG-63 cells, and promote OS cells to proliferate, migrate, and invade. hsa_circ_0000116 was upregulated in OS-derived exosomes, and silencing hsa_circ_0000116 declined the exosome-induced OS cell malignancy. In addition, inhibiting hsa_circ_0000116 effectively inhibited exosome-mediated activation of PI3K/Akt/mTOR and p38/MAPK pathways. In conclusion, exosomal hsa_circ_0000116 can facilitate OS cell malignancy by inducing the activation of PI3K/Akt/mTOR and p38/MAPK pathways. The findings of this study may identify novel molecular mechanisms driving OS progression and provide novel therapeutic targets for OS.