NT5E DNA methylation in papillary thyroid cancer: Novel opportunities for precision oncology

Bertoni, Ana Paula Santin; Valandro, Cleiton; Brasil, Rafael Ávila; Zeiser, Felipe André; Wink, Márcia Rosângela; Furlanetto, Tânia Weber; Costa, Cristiano André da

doi:10.1016/j.mce.2023.111915

Cited by 2 publications

(1 citation statement)

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“…An emerging approach for assessing mutation associations in PTC cell lines involves exploring the epigenetic landscape. Recently, it was demonstrated that the hypomethylation of the cg23172664 site was associated with a BRAF-like phenotype and lower levels of NT5E expression in PTC [ 36 ]. Overall, additional exploration is needed to assess potential associations among specific tumor mutations, such as BRAF, EMT, and adenosinergic pathway.…”

Section: Discussionmentioning

confidence: 99%

CD73 mitigates ZEB1 expression in papillary thyroid carcinoma

Vedovatto,

Oliveira,

Pereira

et al. 2024

Cell Commun Signal

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Background ZEB1, a core transcription factor involved in epithelial-mesenchymal transition (EMT), is associated with aggressive cancer cell behavior, treatment resistance, and poor prognosis across various tumor types. Similarly, the expression and activity of CD73, an ectonucleotidase implicated in adenosine generation, is an important marker of tumor malignancy. Growing evidence suggests that EMT and the adenosinergic pathway are intricately linked and play a pivotal role in cancer development. Therefore, this study focuses on exploring the correlations between CD73 and ZEB1, considering their impact on tumor progression. Methods We employed CRISPR/Cas9 technology to silence CD73 expression in cell lines derived from papillary thyroid carcinoma. These same cells underwent lentiviral transduction of a reporter of ZEB1 non-coding RNA regulation. We conducted studies on cell migration using scratch assays and analyses of cellular speed and polarity. Additionally, we examined ZEB1 reporter expression through flow cytometry and immunocytochemistry, complemented by Western blot analysis for protein quantification. For further insights, we applied gene signatures representing different EMT states in an RNA-seq expression analysis of papillary thyroid carcinoma samples from The Cancer Genome Atlas. Results Silencing CD73 expression led to a reduction in ZEB1 non-coding RNA regulation reporter expression in a papillary thyroid carcinoma-derived cell line. Additionally, it also mitigated ZEB1 protein expression. Moreover, the expression of CD73 and ZEB1 was correlated with alterations in cell morphology characteristics crucial for cell migration, promoting an increase in cell polarity index and cell migration speed. RNA-seq analysis revealed higher expression of NT5E (CD73) in samples with BRAF mutations, accompanied by a prevalence of partial-EMT/hybrid state signature expression. Conclusions Collectively, our findings suggest an association between CD73 expression and/or activity and the post-transcriptional regulation of ZEB1 by non-coding RNA, indicating a reduction in its absence. Further investigations are warranted to elucidate the relationship between CD73 and ZEB1, with the potential for targeting them as therapeutic alternatives for cancer treatment in the near future.

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Section: Discussionmentioning

confidence: 99%