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Research Paper|Volume 11, Issue 23|pp 11609—11623

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

Shenglong Li1, Ke Zheng1, Yi Pei1, Wei Wang1, Xiaojing Zhang1
  • 1Department of Bone and Soft Tissue Tumor Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China
Received: October 11, 2019Accepted: November 20, 2019Published: December 4, 2019
https://doi.org/10.18632/aging.102563

Copyright © 2019 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.