CD73 mitigates ZEB1 expression in papillary thyroid carcinoma
Abstract 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 impl...
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-024-01522-z |
| _version_ | 1827326704574529536 |
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| author | Samlai Vedovatto Fernanda Dittrich Oliveira Luiza Cherobini Pereira Thamiris Becker Scheffel Liziane Raquel Beckenkamp Ana Paula Santin Bertoni Márcia Rosângela Wink Guido Lenz |
| author_facet | Samlai Vedovatto Fernanda Dittrich Oliveira Luiza Cherobini Pereira Thamiris Becker Scheffel Liziane Raquel Beckenkamp Ana Paula Santin Bertoni Márcia Rosângela Wink Guido Lenz |
| author_sort | Samlai Vedovatto |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-07T14:49:18Z |
| format | Article |
| id | doaj.art-1a70ad7e45a6498ca25796fbcf5157eb |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-03-07T14:49:18Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-1a70ad7e45a6498ca25796fbcf5157eb2024-03-05T19:47:08ZengBMCCell Communication and Signaling1478-811X2024-02-0122111110.1186/s12964-024-01522-zCD73 mitigates ZEB1 expression in papillary thyroid carcinomaSamlai Vedovatto0Fernanda Dittrich Oliveira1Luiza Cherobini Pereira2Thamiris Becker Scheffel3Liziane Raquel Beckenkamp4Ana Paula Santin Bertoni5Márcia Rosângela Wink6Guido Lenz7Department of Biophysics, Federal University of Rio Grande do SulDepartment of Biophysics, Federal University of Rio Grande do SulDepartment of Biophysics, Federal University of Rio Grande do SulDepartment of Biophysics, Federal University of Rio Grande do SulDepartment of Basics Health Sciences and Laboratory of Cell Biology, Federal University of Health Sciences of Porto AlegreDepartment of Basics Health Sciences and Laboratory of Cell Biology, Federal University of Health Sciences of Porto AlegreDepartment of Basics Health Sciences and Laboratory of Cell Biology, Federal University of Health Sciences of Porto AlegreDepartment of Biophysics, Federal University of Rio Grande do SulAbstract 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.https://doi.org/10.1186/s12964-024-01522-zCD73ZEB1Papillary thyroid carcinomaEpithelial-mesenchymal plasticityAdenosinergic signaling |
| spellingShingle | Samlai Vedovatto Fernanda Dittrich Oliveira Luiza Cherobini Pereira Thamiris Becker Scheffel Liziane Raquel Beckenkamp Ana Paula Santin Bertoni Márcia Rosângela Wink Guido Lenz CD73 mitigates ZEB1 expression in papillary thyroid carcinoma Cell Communication and Signaling CD73 ZEB1 Papillary thyroid carcinoma Epithelial-mesenchymal plasticity Adenosinergic signaling |
| title | CD73 mitigates ZEB1 expression in papillary thyroid carcinoma |
| title_full | CD73 mitigates ZEB1 expression in papillary thyroid carcinoma |
| title_fullStr | CD73 mitigates ZEB1 expression in papillary thyroid carcinoma |
| title_full_unstemmed | CD73 mitigates ZEB1 expression in papillary thyroid carcinoma |
| title_short | CD73 mitigates ZEB1 expression in papillary thyroid carcinoma |
| title_sort | cd73 mitigates zeb1 expression in papillary thyroid carcinoma |
| topic | CD73 ZEB1 Papillary thyroid carcinoma Epithelial-mesenchymal plasticity Adenosinergic signaling |
| url | https://doi.org/10.1186/s12964-024-01522-z |
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