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Cell Metab. 2010 Oct 6;12(4):352-361. doi: 10.1016/j.cmet.2010.09.002.

miR-378(∗) mediates metabolic shift in breast cancer cells via the PGC-1β/ERRγ transcriptional pathway.

Author information

1
Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montréal, PQ H3G 1Y6, Canada.
2
Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada.
3
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.
4
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.
5
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.

Abstract

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.

PMID:
20889127
DOI:
10.1016/j.cmet.2010.09.002
[Indexed for MEDLINE]
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