miR-378 ∗ Mediates Metabolic Shift in Breast Cancer Cells via the PGC-1β/ERRγ Transcriptional Pathway

• DOI: 10.1016/j.cmet.2010.09.002
• Publication Date: 2010-10-06T08:05:04Z
• Authors: Lillian J. Eichner; Marie-Claude Perry; Catherine R. Dufour; Nicholas Bertos; Morag Park; Julie St-Pierre; Vincent Giguère
• Keywords: Warburg Effect; Anaerobic glycolysis; Bioenergetics

Cancer cell metabolism is often characterized by a shift from an oxidative to a glycolytic bioenergetics pathway, a phenomenon known as the Warburg effect. miR-378(∗) is embedded within PPARGC1b which encodes PGC-1β, a transcriptional regulator of oxidative energy metabolism. Here we show that miR-378(∗) expression is regulated by ERBB2 and induces a metabolic shift in breast cancer cells. miR-378(∗) performs this function by inhibiting the expression of two PGC-1β partners, ERRγ and GABPA, leading to a reduction in tricarboxylic acid cycle gene expression and oxygen consumption as well as an increase in lactate production and in cell proliferation. In situ hybridization experiments show that miR-378(∗) expression correlates with progression of human breast cancer. These results identify miR-378(∗) as a molecular switch involved in the orchestration of the Warburg effect in breast cancer cells via interference with a well-integrated bioenergetics transcriptional pathway.