Research Paper|Volume 12, Issue 14|pp 14157—14173

Circular RNA hsa_circ_0000073 contributes to osteosarcoma cell proliferation, migration, invasion and methotrexate resistance by sponging miR-145-5p and miR-151-3p and upregulating NRAS

Xia Li¹^,*, Yi Liu²^,*, Xiangxin Zhang³, Jun Shen³, Renjie Xu³, Yubo Liu³, Xiao Yu³

¹Department of Orthopaedics, The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’an, Huai’an 223002, People’s Republic of China
²Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, and Shandong Key Laboratory of Oral Tissue Regeneration, and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, and Shenzhen Research Institute of Shandong University, Jinan, Shandong, People’s Republic of China
³Department of Orthopedics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou 215002, People’s Republic of China

* Co-first author

Received: March 14, 2020Accepted: April 28, 2020Published: July 24, 2020

Copyright: © 2020 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

An increasing number of studies have demonstrated that circular RNAs (circRNAs), as promising therapeutic targets, are essential for diverse human diseases, especially cancer. However, the potential functions and complex mechanisms of most circRNAs in osteosarcoma (OS) are still not fully elucidated. In the present study, we obtained the expression profile of circRNAs from a GEO database (GSE96964) and identified hsa_circ_0000073 as a highly expressed candidate in OS. Overexpression of hsa_circ_0000073 accelerated the proliferation, migration, invasion and MTX resistance of OS cells, and knockdown of hsa_circ_0000073 resulted in the opposite effects. Mechanistically, hsa_circ_0000073 upregulated NRAS expression by targeting miR-145-5p and miR-151-3p in OS cells. In addition, the promotion of OS progression by hsa_circ_000007 was blocked by miR-145-5p and miR-151-3p-mediated NRAS inhibition. In conclusion, hsa_circ_0000073 facilitated the proliferation, migration, invasion and MTX resistance of OS cells through the inhibition of miR-145-5p and miR-151-3p-mediated downregulation of NRAS.