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MicroRNAs01:22

MicroRNAs

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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
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Invasive Behavior of Human Breast Cancer Cells in Embryonic Zebrafish
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miRNAs from Zebrafish Embryo Extracts Inhibit Breast Cancer Invasiveness and Migration by Modulating miR-218-5p/PI3K

Noemi Monti1,2, Daniele Antinori1, Sara Proietti2

  • 1Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy.

International Journal of Molecular Sciences
|May 7, 2025
PubMed
Summary
This summary is machine-generated.

Zebrafish embryo extracts (ZFEs) containing specific microRNAs (miRNAs) inhibit triple-negative breast cancer cell invasion. ZFEs reactivate miR-218-5p, downregulating PI3K and reversing malignant phenotypes by restoring phosphoinositide balance and antagonizing epithelial-mesenchymal transition.

Keywords:
E-cadherinPI3Kembryo morphogenetic factorsepithelial–mesenchymal transitionmiR-218-5pmicroRNAstumor reversion

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Area of Science:

  • Developmental Biology
  • Cancer Biology
  • Molecular Biology

Background:

  • Triple-negative breast cancer (TNBC) is aggressive with limited treatment options.
  • MicroRNAs (miRNAs) play crucial roles in regulating gene expression and cellular processes.
  • Zebrafish embryos (ZFEs) are a model organism with unique developmental pathways.

Purpose of the Study:

  • To investigate the potential of zebrafish embryo extracts (ZFEs) as a therapeutic agent against triple-negative breast cancer.
  • To elucidate the molecular mechanisms by which ZFEs affect cancer cell behavior, focusing on miRNA modulation.
  • To determine if ZFEs can inhibit cancer cell invasiveness and motility.

Main Methods:

  • Extraction and purification of soluble factors and miRNAs from distinct zebrafish embryo development phases.
  • Treatment of normal and cancerous breast cells with ZFE-derived miRNA fractions.
  • Analysis of miRNA expression profiles, including miR-218-5p.
  • Assessment of cell invasiveness, motility, and phenotypic changes.
  • Investigation of downstream signaling pathways, including PI3K/phosphoinositides and the TCTP-p53 axis.
  • Evaluation of epithelial-mesenchymal transition (EMT) markers and E-cadherin/β-catenin complex formation.

Main Results:

  • ZFEs exhibit a distinct miRNA profile and modulate miRNA expression in breast cells.
  • ZFEs significantly inhibit the invasiveness and motility of triple-negative breast cancer cells.
  • ZFEs reactivate endogenous miR-218-5p in cancer cells, leading to PI3K downregulation and altered phosphoinositide distribution (PIP2/PIP3).
  • Silencing miR-218-5p abrogated the inhibitory effects of ZFEs.
  • Restoration of proper PIP2/PIP3 ratios promoted malignant phenotype regression, characterized by cytoskeleton rearrangement and E-cadherin/β-catenin complex re-emergence.
  • ZFEs antagonize EMT by modulating pathways including the TCTP-p53 axis.

Conclusions:

  • Zebrafish embryo extracts, enriched with specific miRNAs, can reprogram cancer cells.
  • Reactivation of endogenous miR-218-5p by ZFEs is a key mechanism for inhibiting breast cancer progression and metastasis.
  • ZFEs offer a novel therapeutic strategy by targeting critical pathways involved in tumor malignancy.