Journal Article

hsa_circ_0058122 knockdown prevents steroid‐induced osteonecrosis of the femoral head by inhibiting human umbilical vein endothelial cells apoptosis via the miR‐7974/IGFBP5 axis

Ding, Zhen‐Fei, Wang, Lei, Yin, Zong‐Sheng, Yao, Tao

2022

Overview

Background Steroid‐induced osteonecrosis of femoral head (SONFH) is a serious complication of glucocorticoid overused. Recent evidence has demonstrated that circRNAs exert key pathophysiological roles in a variety of disease processes. However, the role of circRNA in SONFH remains largely unknown. The current study sought to evaluate how hsa_circ_0058122 affects SONFH in dexamethasone (DEX) treated human umbilical vein endothelial cells (HUVECs) model. Methods RT‐PCR was used to demonstrate the hsa_circ_0058122 expression level in Dex‐treated HUVECs cells. The effects of hsa_circ_0058122 on HUVECs apoptosis were evaluated via overexpression plasmid and siRNA. Using dual‐luciferase and fluorescence in situ hybridization assays, we demonstrated that hsa_circ_0058122 binds to miR‐7974 thereby facilitating HUVECs apoptosis. Bioinformatics analysis and western blot were performed to confirm target genes of hsa‐miR‐7974. Results In our previous work, we revealed the top 20 elevated circRNAs in SONFH patients were hsa_circ_0010027, hsa_circ_0058115, hsa_circ_0010026, hsa_circ_0058839, hsa_circ_0056886, hsa_circ_0056885, hsa_circ_0058146, hsa_circ_0058105, hsa_circ_0058112, hsa_circ_0058143, hsa_circ_0058102, hsa_circ_0058090, hsa_circ_0075353, hsa_circ_0058126, hsa_circ_0058130, hsa_circ_0058140, hsa_circ_0058122, hsa_circ_0058123, hsa_circ_0058103, and hsa_circ_0058121. Among these, hsa_circ_0058122 was finally selected for further investigation. We found hsa_circ_0058122 expression was markedly elevated in Dex‐treated HUVECs cells, and the Dex‐mediated HUVEC apoptosis was impaired in hsa_circ_0058122‐silenced cells and increased in hsa_circ_0058122‐overexpressing cells. hsa_circ_0058122 competitively binds to hsa‐miR‐7974, which in turn interacts with insulin‐like growth factor binding protein 5 (IGFBP5). Conclusions hsa_circ_0058122/miR‐7974/IGFBP5 was proposed to be a key regulatory pathway for SONFH. DEX treatment upregulated hsa_circ_0058122 expression in HUVECs, which sponged miR‐7974, thereby increasing IGFBP5 expression, the hsa_circ_0058122/miR‐7974/IGFBP5 axis contributed to the Dex‐mediated apoptosis. These findings may identify novel targets for SONFH molecular therapy. The dexamethasone‐mediated human umbilical vein endothelial cell apoptosis was increased in circFN1‐overexpressing cells and impaired in circFN1‐silenced cells.

• Publisher: John Wiley & Sons, Inc
• Subject: Apoptosis / Apoptosis - genetics / Binding sites / Bioinformatics / blood supply / Cell Proliferation / Cells, Cultured / Dexamethasone / Endothelial cells / Femur / Femur Head - metabolism / Fluorescence in situ hybridization / Glucocorticoids / hsa_circ_0058122 / Human Umbilical Vein Endothelial Cells - metabolism / Humans / In Situ Hybridization, Fluorescence / Insulin / Insulin-Like Growth Factor Binding Protein 5 - genetics / Insulin-Like Growth Factor Binding Protein 5 - metabolism / Insulin-Like Growth Factor Binding Protein 5 - pharmacology / Insulin-like growth factor-binding protein 5 / MicroRNAs - genetics / MicroRNAs - metabolism / miR‐7974 / Osteonecrosis / Osteonecrosis - metabolism / Pathogenesis / Patients / RNA, Circular - genetics / siRNA / SONFH / Steroids / Steroids - metabolism / Steroids - pharmacology / Umbilical vein / Veins & arteries