1. Academic Validation
  2. Circ-STC2 promotes the ferroptosis of nucleus pulposus cells via targeting miR-486-3p/TFR2 axis

Circ-STC2 promotes the ferroptosis of nucleus pulposus cells via targeting miR-486-3p/TFR2 axis

  • J Orthop Surg Res. 2023 Jul 21;18(1):518. doi: 10.1186/s13018-023-04010-1.
Liangping Xiong 1 2 Xiaoyan Li 3 Xi Hua 1 Zhonglai Qian 4
Affiliations

Affiliations

  • 1 Department of Orthopedic Surgery, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215006, Jiangsu, China.
  • 2 Department of Orthopedic Surgery, The First People's Hospital of Jiande, Hangzhou, China.
  • 3 Department of Orthopedic Surgery, Affiliated Hospital of Jining Medical University, Jining, China.
  • 4 Department of Orthopedic Surgery, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215006, Jiangsu, China. qzhonglai@hotmail.com.
Abstract

Background: Low back pain (LBP) has become the second leading cause of disability worldwide, which has brought great economic burden to people. It is generally believed that intervertebral disc degeneration (IDD) is the main cause of LBP. This study aimed to explore the role of circ-STC2 in the pathogenesis of IDD.

Methods: Nucleus pulposus cells (NPCs) were treated with T-Butyl Hydrogen Peroxide (TBHP) to establish IDD model in vitro. RT-qPCR was performed to detect mRNA expressions. The cell viability was detected with CCK-8 assay. The levels of Lactate Dehydrogenase (LDH), malondialdehyde (MDA), Fe2+ and glutathione (GSH) of NPCs were measured by corresponding kits. The protein expressions were determined by western blot. Dual-luciferase reporter and RNA pull-down assays were conducted to verify the relationship between circ-STC2 or transferrin recepto 2 (TFR2) and miR-486-3p.

Results: Circ-STC2 and TFR2 expressions were up-regulated in IDD tissues, and miR-486-3p expression was down-regulated. Knockdown of circ-STC2 promoted the cell viability and inhibited the Ferroptosis of the NPCs. The GSH levels, and Glutathione Peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) protein expressions were increased, the LDH, MDA and Fe2+ levels and achaete-scute complexlike 4 (ASCL4) protein expressions were decreased after circ-STC2 knockdown. Knockdown of miR-486-3p abrogated the si-circ-STC2 effects and overexpression of TFR2 reversed the miR-486-3p mimic effects.

Conclusions: Circ-STC2 inhibits the cell viability, induced the Ferroptosis of the TBHP treated NPCs via targeting miR-486-3p/TFR2 axis.

Keywords

Circ-STC2; Ferroptosis; Intervertebral disc degeneration; Nucleus pulposus cell; TFR2.

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