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-1b, 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-1b partners, ERRg 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.
Updated on July 12, 2020