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Mechanism of SMYD2 promoting stemness maintenance of bladder cancer stem cells by regulating PYCR1 expression and PINK1/Parkin mitophagy pathway

  • Authors:
    • Junjie Chen
    • Shuai Xiao
    • Xieyu Yan
    • Yongbao Wei
    • Wei Song
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410011, P.R. China, Shengli Clinical Medical College of Fujian Medical University, Department of Urology, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian 350001, P.R. China
    Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 41
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    Published online on: May 6, 2025
       https://doi.org/10.3892/ijo.2025.5747
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Abstract

SET and MYND domain‑containing protein 2 (SMYD2), an identified protein‑lysine methyltransferase, is key for bladder cancer (BC) progression. The tumor‑formation capacity and metastatic potential of bladder cancer stem cells (BCSCs) are due to their stemness characteristics. The present study explores the mechanism of SMYD2 in promoting BCSC stemness maintenance by pyrroline‑5‑carboxylate reductase 1 (PYCR1). BC cells were treated with PYCR1, SMYD2 and putative kinase 1 (PINK1) small interfering (si)RNA, pcDNA3.1‑PYCR1 and pcDNA3.1‑SMYD2. Mito‑Tracker Green and light chain‑3B (LC3B) expression, in vitro colony formation ability and tumor stemness were assessed, as well as histone H3 lysine 4 trimethylation (H3K4me3) enrichment and PYCR1, SMYD2, H3K4me3, LC3B II/I, p62, PINK1, Parkin, Nanog and SRY‑box transcription factor 2 (Sox2) expression. A nude mouse xenograft model was used for in vivo verification. PYCR1 mRNA and protein expression were elevated in BCSCs. Following PYCR1 or SMYD2 siRNA treatment, PYCR1, SMYD2 and CD44+CD33+ expression, cancer cell colony formation, number of tumor spheres and Nanog and Sox2 expression were decreased, but pcDNA3.1‑PYCR1 or pcDNA3.1‑SMYD2 transfection enhanced BCSC stemness maintenance. SMYD2 was associated with PYCR1 expression. SMYD2 upregulated PYCR1 expression through H3K4me3, subsequently activating the PINK1/Parkin mitophagy pathway, which supports maintenance of BCSC stemness.
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Copy and paste a formatted citation
Spandidos Publications style
Chen J, Xiao S, Yan X, Wei Y and Song W: Mechanism of SMYD2 promoting stemness maintenance of bladder cancer stem cells by regulating PYCR1 expression and PINK1/Parkin mitophagy pathway. Int J Oncol 66: 41, 2025.
APA
Chen, J., Xiao, S., Yan, X., Wei, Y., & Song, W. (2025). Mechanism of SMYD2 promoting stemness maintenance of bladder cancer stem cells by regulating PYCR1 expression and PINK1/Parkin mitophagy pathway. International Journal of Oncology, 66, 41. https://doi.org/10.3892/ijo.2025.5747
MLA
Chen, J., Xiao, S., Yan, X., Wei, Y., Song, W."Mechanism of SMYD2 promoting stemness maintenance of bladder cancer stem cells by regulating PYCR1 expression and PINK1/Parkin mitophagy pathway". International Journal of Oncology 66.5 (2025): 41.
Chicago
Chen, J., Xiao, S., Yan, X., Wei, Y., Song, W."Mechanism of SMYD2 promoting stemness maintenance of bladder cancer stem cells by regulating PYCR1 expression and PINK1/Parkin mitophagy pathway". International Journal of Oncology 66, no. 5 (2025): 41. https://doi.org/10.3892/ijo.2025.5747
Copy and paste a formatted citation
x
Spandidos Publications style
Chen J, Xiao S, Yan X, Wei Y and Song W: Mechanism of SMYD2 promoting stemness maintenance of bladder cancer stem cells by regulating PYCR1 expression and PINK1/Parkin mitophagy pathway. Int J Oncol 66: 41, 2025.
APA
Chen, J., Xiao, S., Yan, X., Wei, Y., & Song, W. (2025). Mechanism of SMYD2 promoting stemness maintenance of bladder cancer stem cells by regulating PYCR1 expression and PINK1/Parkin mitophagy pathway. International Journal of Oncology, 66, 41. https://doi.org/10.3892/ijo.2025.5747
MLA
Chen, J., Xiao, S., Yan, X., Wei, Y., Song, W."Mechanism of SMYD2 promoting stemness maintenance of bladder cancer stem cells by regulating PYCR1 expression and PINK1/Parkin mitophagy pathway". International Journal of Oncology 66.5 (2025): 41.
Chicago
Chen, J., Xiao, S., Yan, X., Wei, Y., Song, W."Mechanism of SMYD2 promoting stemness maintenance of bladder cancer stem cells by regulating PYCR1 expression and PINK1/Parkin mitophagy pathway". International Journal of Oncology 66, no. 5 (2025): 41. https://doi.org/10.3892/ijo.2025.5747
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