ArticleCell death & disease2021
Phosphoglycerate kinase 1 silencing by a novel microRNA microRNA-4523 protects human osteoblasts from dexamethasone through activation of Nrf2 signaling cascade.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Glycolysis in bone remodeling: from energy supply to signaling regulation.Molecular biology reports · 2026Review
- Review
- Proline-rich 15 depletion enhances Nrf2 cascade to promote osteoblast survival from oxidative injury.Communications biology · 2025Article
- Targeting POLRMT by a first-in-class inhibitor IMT1 inhibits osteosarcoma cell growth in vitro and in vivo.Cell death & disease · 2024Article
- Noncoding RNAs: the crucial role of programmed cell death in osteoporosis.Frontiers in cell and developmental biology · 2024Review
- HOXC13-driven TIMM13 overexpression promotes osteosarcoma cell growth.Cell death & disease · 2023Article
- ZIM3 activation of CCL25 expression in pulmonary metastatic nodules of osteosarcoma recruits M2 macrophages to promote metastatic growth.Cancer immunology, immunotherapy : CII · 2023Article
- The Role of the miR-548au-3p/CA12 Axis in Tracheal Chondrogenesis in Congenital Pulmonary Airway Malformations.Oxidative medicine and cellular longevity · 2023Article
- An Axis between the Long Non-Coding RNAInternational journal of molecular sciences · 2022Article
- Nrf2 signaling activation by a small molecule activator compound 16 inhibits hydrogen peroxide-induced oxidative injury and death in osteoblasts.Cell death discovery · 2022Article
- The requirement of phosphoenolpyruvate carboxykinase 1 for angiogenesis in vitro and in vivo.Science advances · 2022Article
- PGK1: A Common Biomarker and Therapeutic Target Linking Sarcopenia and Osteoporosis Through Fibroblast-Mediated Pathways.IET systems biologyArticle
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Authors and funding
6 authors at 3 institutions in 1 country.
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Abstract
Nuclear-factor-E2-related factor 2 (Nrf2) cascade activation can ameliorate dexamethasone (DEX)-induced oxidative injury and death in human osteoblasts. Phosphoglycerate kinase 1 (PGK1) depletion is shown to efficiently activate Nrf2 signaling by inducing methylglyoxal modification of Kelch-like ECH-associated protein 1 (Keap1). We here identified a novel PGK1-targeting microRNA: microRNA-4523 (miR-4523). RNA fluorescent in situ hybridization, RNA pull-down, and Argonaute-2 RNA immunoprecipitation results confirmed a direct binding between miR-4523 and PGK1 mRNA in primary human osteoblasts and hFOB1.19 osteoblastic cells. Forced overexpression of miR-4523, using a lentiviral construct, robustly decreased PGK1 3'-UTR (untranslated region) luciferase activity and downregulated its expression in human osteoblasts and hFOB1.19 cells. Furthermore, miR-4523 overexpression activated the Nrf2 signaling cascade, causing Keap1-Nrf2 disassociation, Nrf2 protein stabilization, and its nuclear translocation as well as transcription activation of Nrf2-dependent genes (NQO1, GCLC, and HO1) in human osteoblasts. By expressing a UTR-null PGK1 construct, miR-4523 overexpression-induced Nrf2 cascade activation was however largely inhibited. Importantly, DEX-induced reactive oxygen species production, oxidative injury, and cell apoptosis were significantly attenuated by miR-4523 overexpression in human osteoblasts and hFOB1.19 cells. Such actions by miR-4523 were abolished by Nrf2 shRNA or knockout, but mimicked by PGK1 knockout (using CRISPR/Cas9 method). In PGK1 knockout human osteoblasts, miR-4523 overexpression failed to further increase Nrf2 cascade activation and offer osteoblast cytoprotection against DEX. Significantly, miR-4523 is downregulated in human necrotic femoral head tissues of DEX-taking patients. Together, PGK1 silencing by miR-4523 protected human osteoblasts from DEX through activation of the Nrf2 signaling cascade.
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