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.

EGCG Disrupts the LIN28B/Let-7 Interaction and Reduces Neuroblastoma Aggressiveness / 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; Sturlese, Mattia; Sechi, Mario; Aveic, Sanja; Mancini, Ines; Sighel, Denise; Quattrone, Alessandro. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 25:9(2024), pp. 479501-479521. [10.3390/ijms25094795]

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

Cocchi, Simona;Greco, Valentina;Sidarovich, Viktoryia;Vigna, Jacopo;Broso, Francesca;Zasso, Jacopo;Re, Angela;Rosatti, Emanuele Filiberto;Longhi, Sara;Defant, Andrea;Adami, Valentina;D'Agostino, Vito;Mancini, Ines;Sighel, Denise;Quattrone, Alessandro
2024-01-01

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.
2024
9
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; Sturlese, Mattia; Sechi, Mario; Aveic, Sanja; Mancini, Ines; Sighel, Denise; Quattrone, Alessandro
EGCG Disrupts the LIN28B/Let-7 Interaction and Reduces Neuroblastoma Aggressiveness / 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; Sturlese, Mattia; Sechi, Mario; Aveic, Sanja; Mancini, Ines; Sighel, Denise; Quattrone, Alessandro. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 25:9(2024), pp. 479501-479521. [10.3390/ijms25094795]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/411250
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