Expression of Long Noncoding RNA <i>YIYA</i> Promotes Glycolysis in Breast Cancer.

Abstract

Long noncoding RNA (lncRNA) is yet to be linked to cancer metabolism. Here, we report that upregulation of the lncRNA <i>LINC00538</i> (<i>YIYA</i>) promotes glycolysis, cell proliferation, and tumor growth in breast cancer. YIYA is 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 <i>YIYA</i> or CDK6 silencing impaired glycolysis and tumor growth <i>in vivo</i> In clinical specimens of breast cancer, <i>YIYA</i> was expressed in approximately 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.<b>Significance:</b> These findings offer a first glimpse into how a long-coding RNA influences cancer metabolism to drive tumor growth. <i>Cancer Res; 78(16); 4524-32. ©2018 AACR</i>.