Research Paper
Circular RNA LPAR3 enhances GPX4 expression by targeting miR-196a-5p to suppress ferroptosis of osteosarcoma cells
- 1 Department of Orthopaedics, Linyi People's Hospital, Linyi, Shandong Province, China
- 2 Department of Orthopaedics, Jinan People's Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, China
- 3 Department of Cardiology, Jinan People's Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, China
- 4 Central Sterile Supply Department, Linyi People's Hospital, Linyi, Shandong Province, China
Received: April 14, 2021 Accepted: July 30, 2021
https://doi.org/10.18632/aging.203486How to Cite
Copyright: © 2021 Cao 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
Osteosarcoma is a prevalent bone malignancy that presents a low survival rate and high incidence of metastasis. Circular RNAs (circRNAs) have been identified as the critical regulators in osteosarcoma pathogenesis. Here, we reported an innovative function of circular RNA LPAR3 (circLPAR3) in controlling the ferroptosis of osteosarcoma cells. The expression of circLPAR3 was increased in clinical osteosarcoma samples and osteosarcoma cell lines. The proliferation and invasion/migration were repressed, but the apoptosis was induced in osteosarcoma cells by the inhibition of circLPAR3 in vitro, and circLPAR3 knockdown reduced the tumor growth of osteosarcoma in vivo. Specifically, the treatment of ferroptosis activator termed erastin suppressed the cell proliferation, and circLPAR3 shRNA further reinforced this effect in the osteosarcoma cells. Besides, the levels of iron, Fe2+, and ROS were significantly increased by circLPAR3 suppression in the cells. GPX4 reconstitution could reverse circLPAR3 knockdown-induced ferroptosis of osteosarcoma cells. circLPAR3 activated GPX4 expression by sponging miR-196a-5p in the cells. MiR-196a-5p contributed to osteosarcoma cell ferroptosis by targeting GPX4. The circLPAR3 inhibition-attenuated malignant phenotypes of osteosarcoma cells were rescued by the overexpression of GPX4 or miR-196a-5p inhibitor. Consequently, we concluded that circular RNA circLPAR3 enhanced GPX4 expression through sponging miR-196a-5p to suppress ferroptosis in osteosarcoma development. CircLPAR3 and miR-196a-5p may serve as promising targets for osteosarcoma therapy.