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CDH3-AS1 antisense RNA enhances P-cadherin translation and acts as a tumor suppressor in melanoma

Manon Chadourne1, Crystal Griffith1, Neel Jasani1

  • 1Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.

Cell Reports
|October 2, 2025
PubMed

Insights

Antisense RNAs (asRNAs) regulate gene expression in melanoma. CDH3-AS1, an asRNA, enhances P-cadherin translation, suppressing tumor growth and cell adhesion.

Area of Science:

  • Molecular Biology
  • Genomics
  • Cancer Research

Background:

  • Thousands of regulatory non-coding RNAs (ncRNAs) are known, but their roles in gene regulation and cancer progression are not fully understood.
  • ncRNAs constitute a significant portion of deregulated genes during melanoma progression, with antisense RNAs (asRNAs) being particularly prevalent.

Purpose of the Study:

  • To investigate the role of ncRNAs, specifically asRNAs, in melanoma progression.
  • To elucidate the function of CDH3-AS1, a downregulated asRNA, and its impact on P-cadherin expression and melanoma development.

Main Methods:

  • Expression profiling of ncRNAs during melanoma progression.
  • Functional studies involving CDH3-AS1 overexpression in melanoma models.
  • Analysis of CDH3-AS1 interaction with CDH3 mRNA and its effect on translation.

Main Results:

  • ncRNAs comprised nearly half of deregulated genes in melanoma, with asRNAs being a major component.
  • CDH3-AS1, the most downregulated asRNA, was found to interact with CDH3 mRNA, increasing ribosome occupancy and enhancing P-cadherin translation.
  • Overexpression of CDH3-AS1 promoted cell aggregation and reduced tumor growth in xenografts, similar to CDH3's effects.

Conclusions:

  • CDH3-AS1 acts as a tumor suppressor in melanoma by enhancing P-cadherin translation.
  • asRNAs complementary to 5' UTRs can broadly regulate protein translation, suggesting a significant role in gene regulation.
Keywords:
CDH3CDH3-AS1CP: CancerCP: Molecular biologyP-cadherinSINEUPasRNAmelanoma

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