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Regulatory Mechanisms of SPARC Overexpression in Melanoma Progression

  • 0TGF-β and Cancer Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), Hospital Duran i Reynals, L'Hospitalet de Llobregat, 08908 Barcelona, Spain.
International Journal of Molecular Sciences +

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September 13, 2025

|

September 13, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Melanoma progression involves increased SPARC expression, driven by transcription factors PRRX1 and TCF7L2-Sp1. MicroRNA miR-29b1~a fine-tunes SPARC levels, impacting melanoma cell phenotype and metastasis.

Area Of Science

  • Oncology
  • Molecular Biology
  • Genetics

Background

  • Secreted Protein, Acidic and Rich in Cysteine (SPARC) expression elevates during melanoma progression.
  • SPARC upregulation correlates with epithelial-to-mesenchymal transition (EMT), a key factor in melanoma metastasis.
  • The molecular mechanisms governing SPARC expression in melanoma remain largely unknown.

Purpose Of The Study

  • To elucidate the molecular mechanisms controlling SPARC gene expression in human melanoma.
  • To identify key transcription factors and regulatory elements involved in SPARC upregulation during melanoma progression.
  • To investigate the role of microRNAs in modulating SPARC expression and melanoma cell phenotype.

Main Methods

  • Identified PRRX1 as a transcriptional activator of SPARC through promoter binding assays.
  • Correlated SPARC and PRRX1 expression in clinical melanoma samples and cell lines.
  • Investigated the role of TCF7L2 and Sp1 in binding to the SPARC promoter.
  • Analyzed the regulatory relationship between miR-29 family members and SPARC expression.

Main Results

  • Paired-related homeobox 1 (PRRX1), an EMT transcription factor, directly binds to the SPARC promoter, activating its transcription.
  • A significant positive correlation exists between SPARC and PRRX1 expression in melanoma.
  • TCF7L2 and Sp1 bind the SPARC promoter, enhancing expression during the phenotypic switch to a mesenchymal state.
  • SPARC is a direct target of the miR-29 family; miR-29b1~a expression is inversely correlated with SPARC levels and reduced in mesenchymal melanoma.

Conclusions

  • SPARC expression in melanoma is transcriptionally activated by PRRX1, TCF7L2, and Sp1.
  • MiR-29b1~a acts as a negative regulator of SPARC, fine-tuning melanoma cell phenotypic transitions.
  • Understanding these regulatory mechanisms offers potential therapeutic targets for melanoma metastasis.

Keywords:

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