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https://hdl.handle.net/2445/223486
Title: | Regulatory Mechanisms of SPARC Overexpression in Melanoma Progression |
Author: | Vinyals, Antònia Ferreres Riera, Jose Ramon Campos Martín, Rafael Jorge Torres, Olga C. Mainez Villoro, Jessica Puig Butillé, Joan Anton Marcoval Caus, Joaquim Puig i Sardà, Susana Fabregat Romero, Isabel Fabra Fres, Àngels |
Keywords: | Melanoma Oncogens Metàstasi Melanoma Oncogenes Metastasis |
Issue Date: | 8-Sep-2025 |
Publisher: | MDPI |
Abstract: | The expression of the Secreted Protein, Acidic and Rich in Cysteine (SPARC) gene in human melanoma increases during progression and is associated with epithelial-to-mesenchymal transition (EMT), which is a major determinant of metastasis in melanoma patients. However, the underlying molecular mechanisms that control SPARC expression in this context remain elusive. Herein, we identified Paired-related homeobox 1 (PRRX1), an EMT transcription factor, as a transcriptional activator of SPARC by direct binding to the promoter, thereby increasing its activity. Moreover, we found a strong positive correlation between SPARC and PRRX1 expression levels in clinical samples and cell lines. Furthermore, the switch from the proliferative/melanocytic phenotype toward the invasive/mesenchymal-like phenotype favors the expression of TCF7L2, a beta-catenin cofactor, which, together with Sp1, binds to the proximal SPARC promoter, thereby bolstering protein expression. We also show that SPARC is a target of the miR-29 family, whose members are expressed in clinical melanoma samples and cell lines. Indeed, we found that miR-29b1 similar to a expression is inversely correlated with SPARC levels, and it is significantly reduced in samples with a mesenchymal-like phenotype. Taken together, SPARC expression in melanoma cells relies on transcriptional activation by PRRX1/TCF7L2-Sp1 and is modulated through miR-29b1 similar to a, which provides fine-tuning regulation over the switch between phenotypic states. |
Note: | Reproducció del document publicat a: https://doi.org/10.3390/ijms26178743 |
It is part of: | International Journal of Molecular Sciences, 2025, vol. 26, num. 17, 8743 |
URI: | https://hdl.handle.net/2445/223486 |
Related resource: | https://doi.org/10.3390/ijms26178743 |
ISSN: | 1422-0067 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona)) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) |
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ijms-26-08743-v2.pdf | 11.56 MB | Adobe PDF | View/Open |
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