Back to Search
Start Over
EGCG Disrupts the LIN28B/Let-7 Interaction and Reduces Neuroblastoma Aggressiveness.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2024 Apr 27; Vol. 25 (9). Date of Electronic Publication: 2024 Apr 27. - Publication Year :
- 2024
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 25
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 38732012
- Full Text :
- https://doi.org/10.3390/ijms25094795