miR-378(∗) mediates metabolic shift in breast cancer cells via the PGC-1β/ERRγ transcriptional pathway.
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.
Eichner
Lillian J
LJ
Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montréal, PQ H3G 1Y6, Canada.
Perry
Marie-Claude
MC
Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montréal, PQ H3G 1Y6, Canada.
Dufour
Catherine R
CR
Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada.
Bertos
Nicholas
N
Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Breast Cancer Functional Genomic Group and Genomics Core, Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada.
Park
Morag
M
Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Breast Cancer Functional Genomic Group and Genomics Core, Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montréal, PQ H3G 1Y6, Canada; Department of Medicine and Oncology, McGill University, Montréal, PQ H3G 1Y6, Canada.
St-Pierre
Julie
J
Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montréal, PQ H3G 1Y6, Canada.
Giguère
Vincent
V
Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montréal, PQ H3G 1Y6, Canada; Department of Medicine and Oncology, McGill University, Montréal, PQ H3G 1Y6, Canada. Electronic address: vincent.giguere@mcgill.ca.
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D018450:Disease Progression; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D016601:RNA-Binding Proteins; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014158:Transcription, Genetic
D002352:Carrier Proteins; C490917:ESRRG protein, human; C526012:MIRN378 microRNA, human; D035683:MicroRNAs; C455622:PPARGC1B protein, human; D016601:RNA-Binding Proteins; D011960:Receptors, Estrogen