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

Manon Chadourne1, Crystal Griffith1, Xiaonan Xu1

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

Insights

Antisense RNAs (asRNAs) play a key role in melanoma. CDH3-AS1, an asRNA, enhances P-cadherin translation, suppressing tumor growth and offering new therapeutic targets.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Thousands of regulatory noncoding RNAs (ncRNAs) are known, but their roles in gene regulation and cancer are unclear.
  • Melanoma progression involves complex gene regulation, with ncRNAs potentially playing a significant role.

Purpose of the Study:

  • To investigate the influence of ncRNAs on gene regulation during melanoma progression.
  • To identify specific ncRNAs and their functions in melanoma development.

Main Methods:

  • Mapping the landscape of ncRNAs in melanocytes and melanoma cells.
  • Analyzing the expression of ncRNAs and their correlation with gene deregulation.
  • Investigating the function of CDH3-AS1 through overexpression studies and molecular interaction analyses.
  • Utilizing ribosome profiling to understand translational regulation.

Main Results:

  • Nearly half of deregulated genes in melanoma are ncRNAs, with antisense RNAs (asRNAs) being a major component.
  • CDH3-AS1, a downregulated asRNA, overlaps the CDH3 gene (encoding P-cadherin) and its reduced expression correlates with melanoma.
  • Overexpression of CDH3-AS1 suppressed xenograft tumor growth and increased cell aggregation.
  • CDH3-AS1 enhances P-cadherin protein levels by promoting ribosome occupancy on CDH3 mRNA, particularly through interactions with the 5' untranslated region.

Conclusions:

  • CDH3-AS1 acts as a tumor suppressor in melanoma by enhancing P-cadherin translation.
  • Antisense RNAs represent a significant class of gene regulators with potential roles in disease.
  • This study highlights the therapeutic potential of targeting asRNA-mediated translational control in melanoma.

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