Bibliographic Details
Title: |
EGCG Disrupts the LIN28B/Let-7 Interaction and Reduces Neuroblastoma Aggressiveness. |
Authors: |
Cocchi, Simona, Greco, Valentina, Sidarovich, Viktoryia, Vigna, Jacopo, Broso, Francesca, Corallo, Diana, Zasso, Jacopo, Re, Angela, Rosatti, Emanuele Filiberto, Longhi, Sara, Defant, Andrea, Ladu, Federico, Sanna, Vanna, Adami, Valentina, D'Agostino, Vito G., Sturlese, Mattia, Sechi, Mario, Aveic, Sanja, Mancini, Ines, Sighel, Denise |
Source: |
International Journal of Molecular Sciences; May2024, Vol. 25 Issue 9, p4795, 21p |
Subject Terms: |
NEUROBLASTOMA, TUMORS in children, CHILDHOOD cancer, RNA-binding proteins, PEDIATRIC oncology, CHILD death |
Abstract: |
Neuroblastoma (NB) is the most commonly diagnosed extracranial solid tumor in children, accounting for 15% of all childhood cancer deaths. Although the 5-year survival rate of patients with a high-risk disease has increased in recent decades, NB remains a challenge in pediatric oncology, and the identification of novel potential therapeutic targets and agents is an urgent clinical need. The RNA-binding protein LIN28B has been identified as an oncogene in NB and is associated with a poor prognosis. Given that LIN28B acts by negatively regulating the biogenesis of the tumor suppressor let-7 miRNAs, we reasoned that selective interference with the LIN28B/let-7 miRNA interaction would increase let-7 miRNA levels, ultimately leading to reduced NB aggressiveness. Here, we selected (−)-epigallocatechin 3-gallate (EGCG) out of 4959 molecules screened as the molecule with the best inhibitory activity on LIN28B/let-7 miRNA interaction and showed that treatment with PLC/PLGA-PEG nanoparticles containing EGCG (EGCG-NPs) led to an increase in mature let-7 miRNAs and a consequent inhibition of NB cell growth. In addition, EGCG-NP pretreatment reduced the tumorigenic potential of NB cells in vivo. These experiments suggest that the LIN28B/let-7 miRNA axis is a good therapeutic target in NB and that EGCG, which can interfere with this interaction, deserves further preclinical evaluation. [ABSTRACT FROM AUTHOR] |
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Database: |
Complementary Index |
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