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EGCG Disrupts the LIN28B/Let-7 Interaction and Reduces Neuroblastoma Aggressiveness.

Simona Cocchi1, Valentina Greco1, Viktoryia Sidarovich1

  • 1Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, 38123 Trento, Italy.

International Journal of Molecular Sciences
|May 11, 2024
PubMed
Summary

Epigallocatechin gallate (EGCG) delivered via nanoparticles inhibits neuroblastoma (NB) growth by targeting the LIN28B/let-7 miRNA pathway. This approach shows promise for treating aggressive pediatric cancers.

Keywords:
(−)-epigallocatechin 3-gallateAlphaScreenEGCGLIN28B/let-7 interaction inhibitorsPLC/PLGA-PEG nanoparticlesdifferentiation therapyneuroblastomatarget therapy

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Area of Science:

  • Pediatric Oncology
  • Molecular Biology
  • Nanomedicine

Background:

  • Neuroblastoma (NB) is a leading cause of childhood cancer death, with high-risk cases remaining challenging.
  • The oncogene LIN28B promotes NB progression by suppressing tumor suppressor let-7 miRNAs.
  • Targeting the LIN28B/let-7 miRNA axis presents a potential therapeutic strategy for NB.

Purpose of the Study:

  • To identify agents that interfere with the LIN28B/let-7 miRNA interaction to inhibit NB.
  • To evaluate the efficacy of epigallocatechin gallate (EGCG) loaded nanoparticles in preclinical NB models.

Main Methods:

  • Screening of 4959 molecules to identify LIN28B/let-7 miRNA inhibitors.
  • Formulation of EGCG into PLC/PLGA-PEG nanoparticles (EGCG-NPs).
  • Assessment of EGCG-NP effects on let-7 miRNA levels, NB cell growth, and in vivo tumor formation.

Main Results:

  • EGCG demonstrated potent inhibition of the LIN28B/let-7 miRNA interaction.
  • EGCG-NPs increased mature let-7 miRNA levels in NB cells.
  • EGCG-NP treatment inhibited NB cell growth and reduced tumor formation in vivo.

Conclusions:

  • The LIN28B/let-7 miRNA pathway is a viable therapeutic target in neuroblastoma.
  • EGCG, delivered via nanoparticles, shows significant preclinical efficacy against NB.
  • Further investigation of EGCG-NPs is warranted for neuroblastoma treatment.