Long noncoding RNA NR2F1-AS1 enhances the malignant properties of osteosarcoma by increasing forkhead box A1 expression via sponging of microRNA-483-3p

The long noncoding RNA NR2F1-AS1 has been found to promote the development of hepatocellular carcinoma and endometrial cancer. In this study, we measured NR2F1-AS1 expression in osteosarcoma (OS), determined the involvement of NR2F1-AS1 in the malignant properties of OS, and investigated the underlying mechanisms. NR2F1-AS1 was found to be upregulated in OS tumors and cell lines. The increased NR2F1-AS1 level was closely associated with advanced clinical stage and distant metastasis in patients with OS. Patients with OS in an NR2F1-AS1 high-expression group demonstrated significantly shorter overall survival than did patients in an NR2F1-AS1 low-expression group. NR2F1-AS1 knockdown inhibited OS cell proliferation, migration, and invasion and promoted cell cycle arrest and apoptosis in vitro and slowed tumor growth in vivo. NR2F1-AS1 was found to function as a competing endogenous RNA by directly sponging microRNA-483-3p (miR-483-3p) and upregulating its target oncogene forkhead box A1 (FOXA1). Finally, rescue experiments revealed that knockdown of miR-483-3p and recovery of FOXA1 expression both attenuated the influence of the NR2F1-AS1 knockdown on OS cells. Thus, NR2F1-AS1 plays an oncogenic role in OS through sponging miR-483-3p and thereby upregulating FOXA1, suggesting an additional target for osteosarcoma therapeutics.