Expression of long non-coding RNA YIYA promotes glycolysis in breast cancer

Long non-coding RNA (lncRNA) have yet to be linked to cancer metabolism. Here we report that upregulation of the lncRNA LINC00538 (YIYA) promotes glycolysis, cell proliferation and tumor growth in in breast cancer. YIYA associated with the cytosolic cyclin-dependent kinase CDK6 and regulated CDK6-dependent phosphorylation of the fructose bisphosphatase PFK2 (PFKFB3) in a cell cycle-independent manner. In breast cancer cells, these events promoted catalysis of glucose 6-phosphate to fructose-2,6-bisphosphate/fructose-1,6-bisphosphate. CRISPR/Cas9-mediated deletion of YIYA or CDK6 silencing impaired glycolysis and tumor growth in vivo. In clinical specimens of breast cancer, YIYA was expressed in ~40% of cases where it correlated with CDK6 expression and unfavorable survival outcomes. Our results define a functional role for lncRNA in metabolic reprogramming in cancer, with potential clinical implications for its therapeutic targeting.

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