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miR-135a Inhibits the Invasion of Cancer Cells via Suppression of ERRα

Violaine Tribollet1, Bruno Barenton1, Auriane Kroiss1

  • 1Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS UMR5242, Ecole Normale Supérieure de Lyon, Lyon, France.

Plos One
|May 27, 2016
PubMed

Insights

MicroRNA-135a (miR-135a) suppresses cancer progression by down-regulating Estrogen-Related Receptor α (ERRα). Reduced miR-135a in metastatic cancers increases ERRα, promoting cell invasion and poor prognosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • MicroRNA-135a (miR-135a) expression is reduced in metastatic breast and prostate cancers.
  • Estrogen-Related Receptor α (ERRα) expression is elevated in these cancers and correlates with poor prognosis.
  • ERRα promotes cancer aggressiveness, including cell invasion.

Purpose of the Study:

  • To investigate the regulatory relationship between miR-135a and ERRα.
  • To determine the functional impact of this relationship on cancer progression, specifically cell invasion.

Main Methods:

  • Analysis of miR-135a expression in metastatic versus non-metastatic tumors.
  • Luciferase assays to confirm direct targeting of ERRα by miR-135a via its 3'UTR.
  • Assessment of cell invasive potential in response to miR-135a modulation and ERRα dependency.

Main Results:

  • miR-135a directly down-regulates ERRα expression by binding to its 3'UTR.
  • miR-135a reduces the expression of ERRα downstream targets.
  • miR-135a inhibits cancer cell invasion in an ERRα-dependent manner.

Conclusions:

  • Decreased miR-135a in metastatic tumors leads to increased ERRα expression.
  • Elevated ERRα, driven by reduced miR-135a, enhances cancer cell invasion capacity.
  • This miR-135a/ERRα axis represents a potential therapeutic target for aggressive cancers.

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