TBX1 and Basal Cell Carcinoma: Expression and Interactions with Gli2 and Dvl2 Signaling

Caprio, Cinzia; Varricchio, Silvia; Bilio, Marchesa; Feo, Federica; Ferrentino, Rosa; Russo, Daniela; Staibano, Stefania; Alfano, Daniela; Missero, Caterina; Ilardi, Gennaro

doi:10.3390/ijms21020607

“…KEGG pathway analysis showed again a strong enrichment of ECM-related pathways but with some limited overlap with the P19Cl6 results, as both models showed focal adhesion to be among the enriched pathways. The enrichment of the KEGG pathways “ECM-receptor interaction” and “basal cell carcinoma” categories in the mESC model is also consistent with recent findings in the mouse ( Alfano et al, 2019 ; Caprio et al, 2020 ).…”

Section: Resultssupporting

confidence: 90%

Chromatin and Transcriptional Response to Loss of TBX1 in Early Differentiation of Mouse Cells

Cirino

¹

,

Aurigemma

²

,

Franzese

³

et al. 2020

Front. Cell Dev. Biol.

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The T-box transcription factor TBX1 has critical roles in the cardiopharyngeal lineage and the gene is haploinsufficient in DiGeorge syndrome, a typical developmental anomaly of the pharyngeal apparatus. Despite almost two decades of research, if and how TBX1 function triggers chromatin remodeling is not known. Here, we explored genome-wide gene expression and chromatin remodeling in two independent cellular models of Tbx1 loss of function, mouse embryonic carcinoma cells P19Cl6, and mouse embryonic stem cells (mESCs). The results of our study revealed that the loss or knockdown of TBX1 caused extensive transcriptional changes, some of which were cell type-specific, some were in common between the two models. However, unexpectedly we observed only limited chromatin changes in both systems. In P19Cl6 cells, differentially accessible regions (DARs) were not enriched in T-BOX binding motifs; in contrast, in mESCs, 34% (n = 47) of all DARs included a T-BOX binding motif and almost all of them gained accessibility in Tbx1 −/− cells. In conclusion, despite a clear transcriptional response of our cell models to loss of TBX1 in early cell differentiation, chromatin changes were relatively modest.

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“…and "basal cell carcinoma" categories in the mESC model is also consistent with recent findings in the mouse (Alfano et al, 2019;Caprio et al, 2020).…”

Section: Transcriptional Profilingsupporting

confidence: 90%

Chromatin and transcriptional response to loss of TBX1 in early differentiation of mouse cells

Cirino

¹

,

Aurigemma

²

,

Franzese

³

et al. 2020

Preprint

Self Cite

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The T-box transcription factor TBX1 has critical roles in the cardiopharyngeal lineage and the gene is haploinsufficient in DiGeorge syndrome, a typical developmental anomaly of the pharyngeal apparatus. Despite almost two decades of research, if and how TBX1 function triggers chromatin remodeling is not known.Here, we explored genome-wide gene expression and chromatin remodeling in two independent cellular models of Tbx1 loss of function, mouse embryonic carcinoma cells P19Cl6, and mouse embryonic stem cells (mESCs). The results of our study revealed that the loss or knockdown of TBX1 caused extensive transcriptional changes, some of which were cell typespecific, some were in common between the two models. However, unexpectedly we observed only limited chromatin changes in both systems. In P19Cl6 cells, differentially accessible regions (DARs) were not enriched in T-BOX binding motifs; in contrast, in mESCs, 34% (n=47) of all DARs included a T-BOX binding motif and almost all of them gained accessibility in Tbx1 -/cells. In conclusion, despite a clear transcriptional response of our cell models to loss of TBX1 in early cell differentiation, chromatin changes were relatively modest. G. (2011). Stage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines. Cell Stem Cell 8, 228-240. , et al. (2015). 22q11.2 deletion syndrome. Nat. Rev. Dis. Primer 1, 15071. Mueller, I., Kobayashi, R., Nakajima, T., Ishii, M. and Ogawa, K. (2010). Effective and steady differentiation of a clonal derivative of P19CL6 embryonal carcinoma cell line into beating cardiomyocytes. J Biomed Biotechnol 2010, 380561. Okubo, T., Kawamura, A., Takahashi, J., Yagi, H., Morishima, M., Matsuoka, R. and Takada, S. (2011). Ripply3, a Tbx1 repressor, is required for development of the pharyngeal apparatus and its derivatives in mice. Dev. Camb. Engl. 138, 339-348. Quinlan, A. R. and Hall, I. M. (2010). BEDTools: a flexible suite of utilities for comparing genomic features. Bioinforma. Oxf. Engl. 26, 841-842. Raudvere, U., Kolberg, L., Kuzmin, I., Arak, T., Adler, P., Peterson, H. and Vilo, J. (2019). g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update). Nucleic Acids Res. 47, W191-W198. . In vitro modeling of paraxial and lateral mesoderm differentiation reveals early reversibility. Stem Cells Dayt. Ohio 24, 575-586.

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“…Early events of BCC tumorigenesis are triggered by inappropriate activation of SHH signaling. Early events of BCC tumorigenesis are triggered by inappropriate activation of SHH signaling, via the loss of Patched1 ( Ptch1 ) or by activating mutations of Smoothened ( Smo ) [ 41 ]. TBX1 , a transcription factor, is connected to several major signaling systems, such as FGF, WNT, and SHH, and it has been linked to cell proliferation and to the regulation of cell shape and cell dynamics.…”

Section: Discussionmentioning

confidence: 99%

Interaction of Arsenic Exposure and Transcriptomic Profile in Basal Cell Carcinoma

Kibriya

¹

,

Jasmine

²

,

Muñoz

³

et al. 2022

Cancers

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0

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Exposure to inorganic arsenic (As) is recognized as risk factor for basal cell carcinoma (BCC). We have followed-up 7000 adults for 6 years who were exposed to As and had manifest As skin toxicity. Of them, 1.7% developed BCC (males = 2.2%, females = 1.3%). In this study, we compared transcriptome-wide RNA sequencing data from the very first 26 BCC cases and healthy skin tissue from independent 16 individuals. Genes in “ cell carcinoma pathway”, “Hedgehog signaling pathway”, and “Notch signaling pathway” were overexpressed in BCC, confirming the findings from earlier studies in BCC in other populations known to be exposed to As. However, we found that the overexpression of these known pathways was less pronounced in patients with high As exposure (urinary As creatinine ratio (UACR) > 192 µg/gm creatinine) than patients with low UACR. We also found that high UACR was associated with impaired DNA replication pathway, cellular response to different DNA damage repair mechanisms, and immune response. Transcriptomic data were not strongly suggestive of great potential for immune checkpoint inhibitors; however, it suggested lower chance of platinum drug resistance in BCC patients with high UACR compared high platinum drug resistance potential in patients with lower UACR.

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TBX1 and Basal Cell Carcinoma: Expression and Interactions with Gli2 and Dvl2 Signaling

Cited by 10 publications

References 24 publications

Chromatin and Transcriptional Response to Loss of TBX1 in Early Differentiation of Mouse Cells

Chromatin and Transcriptional Response to Loss of TBX1 in Early Differentiation of Mouse Cells

Chromatin and transcriptional response to loss of TBX1 in early differentiation of mouse cells

Interaction of Arsenic Exposure and Transcriptomic Profile in Basal Cell Carcinoma

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