[PDF][PDF] miR-378∗ mediates metabolic shift in breast cancer cells via the PGC-1β/ERRγ transcriptional pathway
Cell metabolism, 2010•cell.com
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 …
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 …
Summary
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.
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