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LncRNA MEG3 suppresses erastin-induced ferroptosis of chondrocytes via regulating miR-885-5p/SLC7A11 axis

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Abstract

Background

Ferroptosis is involved in osteoarthritis development; however, the roles of long noncoding RNAs (lncRNAs), including lncRNA MEG3, in the regulation of ferroptosis in osteoarthritis are still unclear.

Methods

In this study, qRT‒PCR and Western blotting assays were used to detect the expression of lncRNA MEG3, miR-885-5p, SLC7A11 and GPX4; MDA and CCK-8 assays were applied to analyse cellular MDA levels and cell viability, respectively.

Result

Erastin elevated cellular MDA levels and decreased the viability of chondrocytes and the erastin-induced decline in cell viability was reversed by a ferroptosis inhibitor (ferrostatin-1). Erastin downregulated lncRNA MEG3, SLC7A11 and GPX4 and upregulated miR-885-5p. Silencing of lncRNA MEG3 increased miR-885-5p and downregulated SLC7A11 and GPX4 and further sensitized chondrocytes to erastin-induced ferroptosis. In contrast, overexpression of lncRNA MEG3 had opposite effects. Dual luciferase assays confirmed binding between lncRNA MEG3 and miR-885-5p and between miR-885-5p and the 3′UTR of SLC7A11. In the synovial fluids from patients with osteoarthritis compared with synovial fluids from normal controls, the RNA levels of lncRNA MEG3 and SLC7A11 were decreased and the miR-885-5p expression level was increased.

Conclusion

Our findings indicated that lncRNA MEG3 overexpression alleviated ferroptosis in chondrocytes by affecting the miR-885-5p/SLC7A11 signalling pathway.

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Data availability

All data generated or analyzed during this study are included in this published article.

Abbreviations

lncRNAs:

Long noncoding RNAs

OA:

Osteoarthritis

Fer-1:

Ferrostatin-1

Nec-1:

Necrostatin-1

ZVF:

Z-VAD-FMK

MEG3:

Maternally expressed 3

qRT-PCR:

Quantitative real time polymerase chain reaction

SLC7A11:

Solute carrier family 7 member 11

MDA:

Malondialdehyde

CCK-8:

Cell counting kit 8

3′UTR:

3′ Untranslated region

Bax:

BCL2 associated X, apoptosis regulator

IL-1β:

Interleukin-1β

KLF4:

KLF transcription factor 4

FOXO1:

Forkhead box O1

VEGF:

Vascular endothelial growth factor

GPX4:

Glutathione peroxidase 4

MO:

Mild osteoarthritis

SO:

Severe osteoarthritis

DMEM:

Dulbecco’s modified eagle’s medium

FBS:

Fetal bovine serum

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

NC:

Negative control

SMAD7:

SMAD family member 7

ATF3:

Activating transcription factor 3

TFRC:

Transferrin receptor

NCOA4:

Nuclear receptor coactivator 4

AMPKα:

AMP-activated Protein Kinase α

Nrf2:

NF-E2-related factor 2

HO-1:

Heme oxygenase 1

ROS:

Reactive oxygen species

MMP13:

Matrix metallopeptidase 13

iNOS:

Inducible nitric oxide synthase

COX2:

Cytochrome c oxidase subunit II

MB:

Methylene blue

LPS:

Lipopolysaccharides

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Funding

This work was supported by Application base project of Yunnan Science and Technology Department (No. 2019FB097); Yunnan Fundamental Research Key Projects (No. 202101AS070046); Yunnan High-level Scientific and Technological Talent Platform Plan (No. 202105AC160064); Project of Yunnan Province Clinical Research Center for Geriatrics (202102AA310002); Project of Yunnan Province Clinical Research Center for Orthopaedic and Athletic Rehabilitation (202102AA310068); Medical joint special project of Kunming University of Science and Technology (KUST-KH2022004Z); Yunnan Ten Thousand Talents Program for Famous Doctors (YNWR-MY-2018-020).

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Author notes

  1. Chongtao Zhu and Bin Chen have contributed equally to this work.

Authors and Affiliations

  1. Laser Medical Center, The First People’s Hospital of Yunnan Province, Kunming, 650032, China

    Chongtao Zhu

  2. Orthopaedics, The First People’s Hospital of Yunnan Province, Kunming, 650032, China

    Bin Chen

  3. Yunnan Province Clinical Research Center for Geriatrics, The First People’s Hospital of Yunnan Province, Kunming, 650032, China

    Xu He, Weiyuan Li, Yan Li, Ping Wan & Xiaolu Li

  4. Medical School, Kunming University of Science and Technology, Kunming, 650500, China

    Shengyu Wang & Xun Zhu

  5. The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, China

    Chongtao Zhu, Bin Chen, Xu He, Weiyuan Li, Yan Li, Ping Wan & Xiaolu Li

Authors
  1. Chongtao Zhu
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  2. Bin Chen
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Contributions

ZCT and CB performed the experiments; HX, LWY, WSY, ZX and LY analyzed the data; ZCT, WP and LXL wrote the manuscript.

Corresponding authors

Correspondence to Chongtao Zhu, Ping Wan or Xiaolu Li.

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The authors declare no competing interests.

Ethical approval

The Ethical Committee of the First People’s Hospital of Yunnan Province approved the study (2018JC031) and each subject signed the written informed consent. The experiments conform to the Helsinki Declaration.

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Zhu, C., Chen, B., He, X. et al. LncRNA MEG3 suppresses erastin-induced ferroptosis of chondrocytes via regulating miR-885-5p/SLC7A11 axis. Mol Biol Rep 51, 139 (2024). https://doi.org/10.1007/s11033-023-09095-9

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