PUBLICATION
miRNAs from Zebrafish Embryo Extracts Inhibit Breast Cancer Invasiveness and Migration by Modulating miR-218-5p/PI3K Pathway
- Authors
- Monti, N., Antinori, D., Proietti, S., Piombarolo, A., Querqui, A., Lentini, G., Liguoro, D., Aventaggiato, M., Lucarelli, M., Pensotti, A., Giuliani, A., Tafani, M., Fuso, A., Bizzarri, M.
- ID
- ZDB-PUB-250508-2
- Date
- 2025
- Source
- International Journal of Molecular Sciences 26: (Journal)
- Registered Authors
- Keywords
- E-cadherin, PI3K, embryo morphogenetic factors, epithelial?mesenchymal transition, miR-218-5p, microRNAs, tumor reversion
- MeSH Terms
-
- Gene Expression Regulation, Neoplastic
- Cell Line, Tumor
- Cell Movement/drug effects
- Cell Movement/genetics
- Female
- Neoplasm Invasiveness
- Humans
- Phosphatidylinositol 3-Kinases*/genetics
- Phosphatidylinositol 3-Kinases*/metabolism
- Epithelial-Mesenchymal Transition/genetics
- Animals
- Embryo, Nonmammalian/metabolism
- MicroRNAs*/genetics
- MicroRNAs*/metabolism
- Zebrafish*/embryology
- Zebrafish*/genetics
- Signal Transduction
- Breast Neoplasms*/genetics
- Breast Neoplasms*/metabolism
- Breast Neoplasms*/pathology
- PubMed
- 40332412 Full text @ Int. J. Mol. Sci.
Citation
Monti, N., Antinori, D., Proietti, S., Piombarolo, A., Querqui, A., Lentini, G., Liguoro, D., Aventaggiato, M., Lucarelli, M., Pensotti, A., Giuliani, A., Tafani, M., Fuso, A., Bizzarri, M. (2025) miRNAs from Zebrafish Embryo Extracts Inhibit Breast Cancer Invasiveness and Migration by Modulating miR-218-5p/PI3K Pathway. International Journal of Molecular Sciences. 26:.
Abstract
Herein, we demonstrate that soluble factors extracted from the distinct phases of the development of zebrafish embryos (ZFEs) exhibit a specific miRNA profile. We removed proteins and concentrated miRNAs in different phase-related samples, which we investigated further. We observed that ZFEs modulate miRNA expression in both normal and cancerous breast cells, significantly inhibiting the invasiveness and motility of triple-negative breast cancer cells. Namely, ZFEs reactivate the synthesis of miR-218-5p in cancerous cells, leading to the downregulation of PI3K, which consequently alters the distribution of phosphoinositides (such as PIP2/PIP3). Moreover, the silencing of miR-218-5p abolished the ZFE effects. Restoring a proper PIP2/PIP3 ratio is crucial for promoting the regression of the malignant phenotype. Phenotypic reversion follows the extensive cytoskeleton rearrangement and the re-emergence of E-cadherin/β-catenin complexes. In addition, ZFEs antagonize the Epithelial Mesenchymal Transition (EMT) by modulating several pathways, including the TCTP-p53 axis. Overall, these results show that embryo extracts enriched with fish miRNAs reactivate endogenous miR-218-5p in cancerous cells, which in turn downregulates critical pathways involved in tumor progression and metastasis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping