Silencing YTHDF2 Induces Apoptosis of Neuroblastoma Cells In a Cell Line-Dependent Manner via Regulating the

Zhongyan Hua1,2, Baocheng Gong1,2, Zhijie Li3,4

  • 1Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.

Molecular Neurobiology
|February 20, 2025
PubMed

Insights

Retinoic acid (RA) reduces neuroblastoma (NB) cell growth and promotes apoptosis by affecting DLK1 and YTHDF2 expression. DLK1 and YTHDF2 are potential therapeutic targets for NB treatment.

Area of Science:

  • Pediatric Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Neuroblastoma (NB) is a common childhood extracranial solid tumor.
  • Chemoradiotherapy for NB causes significant quality of life issues.
  • Identifying novel therapeutic targets is crucial for improving NB patient outcomes.

Purpose of the Study:

  • To investigate the role of retinoic acid (RA) in regulating neuroblastoma cell proliferation and apoptosis.
  • To explore the relationship between DLK1, YTHDF2, and m6A modification in NB.
  • To evaluate DLK1 and YTHDF2 as potential therapeutic targets for NB.

Main Methods:

  • Utilized NGP, KCNR, and SH-SY5Y (SY5Y) neuroblastoma cell lines.
  • Treated cells with retinoic acid (RA) and silenced DLK1 or YTHDF2 expression using siRNAs.
  • Assessed cell proliferation, apoptosis, and expression of target molecules via IncuCyte ZOOM, RT-qPCR, western blotting, Annexin V/PI staining, Caspase-Glo 3/7 assay, RNA m6A quantification, MeRIP-qPCR, and RIP-qPCR.

Main Results:

  • RA treatment decreased DLK1 and YTHDF2 expression in NB cells; lower DLK1 correlated with better prognosis.
  • Knockdown of DLK1 or YTHDF2 inhibited proliferation and induced apoptosis in SY5Y cells.
  • DLK1 mRNA exhibits m6A modification sites, with increased m6A-modified DLK1 after RA treatment. YTHDF2 regulates DLK1 expression, and YTHDF2-bound DLK1 mRNA levels decreased post-RA treatment.

Conclusions:

  • YTHDF2 may regulate NB cell proliferation and apoptosis via DLK1 mRNA m6A modification in a cell-line-dependent manner.
  • DLK1 and YTHDF2 represent potential therapeutic targets for neuroblastoma patients.

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