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CD73 mitigates ZEB1 expression in papillary thyroid carcinoma.

Samlai Vedovatto1, Fernanda Dittrich Oliveira1, Luiza Cherobini Pereira1

  • 1Department of Biophysics, Federal University of Rio Grande do Sul, Av. Bento Gonçalves, 9500, Prédio 43431, sala 107, UFRGS, Porto Alegre, RS, Brazil.

Cell Communication and Signaling : CCS
|February 22, 2024
PubMed
Summary

This study shows that reducing CD73 levels decreases ZEB1 expression and enhances cell migration in papillary thyroid cancer. Targeting CD73 and ZEB1 may offer new cancer treatment strategies.

Keywords:
Adenosinergic signalingCD73Epithelial-mesenchymal plasticityPapillary thyroid carcinomaZEB1

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Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • ZEB1 is a transcription factor linked to aggressive cancer, treatment resistance, and poor prognosis.
  • CD73, an ectonucleotidase, is a marker of tumor malignancy and involved in adenosine generation.
  • Epithelial-mesenchymal transition (EMT) and the adenosinergic pathway are interconnected in cancer development.

Purpose of the Study:

  • To explore the correlation between CD73 and ZEB1 in papillary thyroid carcinoma.
  • To investigate the impact of CD73 on ZEB1 expression and activity.
  • To understand the combined role of CD73 and ZEB1 in tumor progression.

Main Methods:

  • CRISPR/Cas9 was used to silence CD73 in papillary thyroid carcinoma cell lines.
  • Lentiviral transduction was employed to create a ZEB1 non-coding RNA regulation reporter.
  • Cell migration, speed, polarity, ZEB1 reporter expression, and protein levels were analyzed.
  • RNA-seq analysis of The Cancer Genome Atlas (TCGA) papillary thyroid carcinoma samples was performed.

Main Results:

  • Silencing CD73 reduced ZEB1 non-coding RNA regulation reporter expression and ZEB1 protein levels.
  • CD73 and ZEB1 expression correlated with increased cell migration speed and polarity.
  • RNA-seq showed higher CD73 (NT5E) expression in BRAF-mutated samples with partial-EMT signatures.

Conclusions:

  • CD73 expression is associated with post-transcriptional regulation of ZEB1 by non-coding RNA.
  • The study suggests a reduction in ZEB1 regulation in the absence of CD73.
  • Targeting CD73 and ZEB1 presents potential therapeutic strategies for cancer treatment.