1. EGCG Disrupts the LIN28B/Let-7 Interaction and Reduces Neuroblastoma Aggressiveness.
- Author
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Cocchi S, Greco V, Sidarovich V, Vigna J, Broso F, Corallo D, Zasso J, Re A, Rosatti EF, Longhi S, Defant A, Ladu F, Sanna V, Adami V, D'Agostino VG, Sturlese M, Sechi M, Aveic S, Mancini I, Sighel D, and Quattrone A
- Subjects
- Humans, Animals, Mice, Cell Line, Tumor, Gene Expression Regulation, Neoplastic drug effects, Cell Proliferation drug effects, Xenograft Model Antitumor Assays, Mice, Nude, Catechin analogs & derivatives, Catechin pharmacology, Neuroblastoma genetics, Neuroblastoma pathology, Neuroblastoma metabolism, Neuroblastoma drug therapy, MicroRNAs genetics, MicroRNAs metabolism, RNA-Binding Proteins metabolism, RNA-Binding Proteins genetics
- 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.
- Published
- 2024
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