LncRNA MEG3 suppresses erastin-induced ferroptosis of chondrocytes via regulating miR-885-5p/SLC7A11 axis
Tóm tắt
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. 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. 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. Our findings indicated that lncRNA MEG3 overexpression alleviated ferroptosis in chondrocytes by affecting the miR-885-5p/SLC7A11 signalling pathway.
Tài liệu tham khảo
Fibel KH, Hillstrom HJ, Halpern BC (2015) State-of-the-art management of knee osteoarthritis. World J Clin Cases 3(2):89–101. https://doi.org/10.12998/wjcc.v3.i2.89
March LM, Bagga H (2004) Epidemiology of osteoarthritis in Australia. Med J Aust 180(S5):S6-10. https://doi.org/10.5694/j.1326-5377.2004.tb05906.x
Xiong G, Wang S, Pan Z, Liu N, Zhao D, Zha Z et al (2022) Long non-coding RNA MEG3 regulates the progress of osteoarthritis by regulating the miR-34a/Klotho axis. Ann Transl Med 10(8):454. https://doi.org/10.21037/atm-22-894
Zhou X, Yuan P, Liu Q, Liu Z (2017) LncRNA MEG3 regulates imatinib resistance in chronic myeloid leukemia via suppressing MicroRNA-21. Biomol Ther 25(5):490–496. https://doi.org/10.4062/biomolther.2016.162
Huang Y, Chen D, Yan Z, Zhan J, Xue X, Pan X et al (2021) LncRNA MEG3 protects chondrocytes from IL-1beta-Induced inflammation via regulating miR-9-5p/KLF4 Axis. Front Physiol 12:617654. https://doi.org/10.3389/fphys.2021.617654
Wang A, Hu N, Zhang Y, Chen Y, Su C, Lv Y et al (2019) MEG3 promotes proliferation and inhibits apoptosis in osteoarthritis chondrocytes by miR-361-5p/FOXO1 axis. BMC Med Genomics 12(1):201. https://doi.org/10.1186/s12920-019-0649-6
Su L, Wang Y, Bao Y, Liu X, Xu H (2020) LncRNA MEG3 promotes recovery of knee osteoarthritis in rats through regulating VEGF expression. Panminerva Med. https://doi.org/10.23736/S0031-0808.19.03832-1
Miao Y, Chen Y, Xue F, Liu K, Zhu B, Gao J et al (2022) Contribution of ferroptosis and GPX4’s dual functions to osteoarthritis progression. EBioMedicine 76:103847. https://doi.org/10.1016/j.ebiom.2022.103847
Guo Z, Lin J, Sun K, Guo J, Yao X, Wang G et al (2022) Deferoxamine alleviates osteoarthritis by inhibiting chondrocyte ferroptosis and activating the Nrf2 pathway. Front Pharmacol 13:791376. https://doi.org/10.3389/fphar.2022.791376
Wang X, Liu Z, Peng P, Gong Z, Huang J, Peng H (2022) Astaxanthin attenuates osteoarthritis progression via inhibiting ferroptosis and regulating mitochondrial function in chondrocytes. Chem Biol Interact 366:110148. https://doi.org/10.1016/j.cbi.2022.110148
Ma Q, Dai X, Lu W, Qu X, Liu N, Zhu C (2021) Silencing long non-coding RNA MEG8 inhibits the proliferation and induces the ferroptosis of hemangioma endothelial cells by regulating miR-497-5p/NOTCH2 axis. Biochem Biophys Res Commun 556:72–78. https://doi.org/10.1016/j.bbrc.2021.03.132
Yan J, Feng G, Ma L, Chen Z, Jin Q (2022) Metformin alleviates osteoarthritis in mice by inhibiting chondrocyte ferroptosis and improving subchondral osteosclerosis and angiogenesis. J Orthop Surg Res 17(1):333. https://doi.org/10.1186/s13018-022-03225-y
Xu C, Ni S, Xu N, Yin G, Yu Y, Zhou B et al (2022) Theaflavin-3,3’-digallate inhibits erastin-induced chondrocytes ferroptosis via the Nrf2/GPX4 signaling pathway in osteoarthritis. Oxid Med Cell Longev 2022:3531995. https://doi.org/10.1155/2022/3531995
Xu J, Xu Y (2017) The lncRNA MEG3 downregulation leads to osteoarthritis progression via miR-16/SMAD7 axis. Cell Biosci 7:69. https://doi.org/10.1186/s13578-017-0195-x
Chen K, Zhu H, Zheng MQ, Dong QR (2021) LncRNA meg3 inhibits the degradation of the extracellular matrix of chondrocytes in osteoarthritis via targeting miR-93/TGFBR2 axis. Cartilage 13(2):1274S-1284S. https://doi.org/10.1177/1947603519855759
Al-Hetty H, Abdulameer SJ, Alghazali MW, Sheri FS, Saleh MM, Jalil AT (2023) The role of ferroptosis in the pathogenesis of osteoarthritis. J Membr Biol. https://doi.org/10.1007/s00232-023-00282-0
Wang X, Liu T, Qiu C, Yu S, Zhang Y, Sheng Y et al (2023) Characterization and role exploration of ferroptosis-related genes in osteoarthritis. Front Mol Biosci 10:1066885. https://doi.org/10.3389/fmolb.2023.1066885
Sun K, Hou L, Guo Z, Wang G, Guo J, Xu J et al (2023) JNK-JUN-NCOA4 axis contributes to chondrocyte ferroptosis and aggravates osteoarthritis via ferritinophagy. Free Radic Biol Med 200:87–101. https://doi.org/10.1016/j.freeradbiomed.2023.03.008
He Q, Yang J, Pan Z, Zhang G, Chen B, Li S et al (2023) Biochanin A protects against iron overload associated knee osteoarthritis via regulating iron levels and NRF2/System xc-/GPX4 axis. Biomed Pharmacother 157:113915. https://doi.org/10.1016/j.biopha.2022.113915
Wan Y, Shen K, Yu H, Fan W (2023) Baicalein limits osteoarthritis development by inhibiting chondrocyte ferroptosis. Free Radic Biol Med 196:108–120. https://doi.org/10.1016/j.freeradbiomed.2023.01.006
Gong Z, Wang Y, Li L, Li X, Qiu B, Hu Y (2023) Cardamonin alleviates chondrocytes inflammation and cartilage degradation of osteoarthritis by inhibiting ferroptosis via p53 pathway. Food Chem Toxicol 174:113644. https://doi.org/10.1016/j.fct.2023.113644
Jin Y, Xu M, Zhu H, Dong C, Ji J, Liu Y et al (2021) Therapeutic effects of bone marrow mesenchymal stem cells-derived exosomes on osteoarthritis. J Cell Mol Med 25(19):9281–9294. https://doi.org/10.1111/jcmm.16860
Li X, Tang C, Wang J, Guo P, Wang C, Wang Y et al (2018) Methylene blue relieves the development of osteoarthritis by upregulating lncRNA MEG3. Exp Ther Med 15(4):3856–3864. https://doi.org/10.3892/etm.2018.5918