Circular RNA eukaryotic translation initiation factor-6 motivates aerobic glycolysis and angiogenesis in triple negative breast cancer via performing as the competing endogenous RNA of microRNA-296-3p to target metallothionein 2A.

Triple-negative breast cancer (TNBC) lacks effective therapeutic targets. This study investigated the mechanism by which circular RNA eukaryotic translation initiation factor 6 (circEIF6) regulates TNBC progression via the miR-296-3p/metallothionein 2A (MT2A) axis. Tumor and adjacent tissues from 32 TNBC patients were analyzed. TNBC (MD Anderson Metastatic Breast-231) and non-TNBC (MCF-7) cells were used to assess circEIF6, miR-296-3p, and MT2A expression. Functional assays measured glycolysis (including glucose uptake, lactate production, adenosine triphosphate levels, extracellular acidification rate/oxygen consumption rate), angiogenesis (anti-vascular endothelial growth factor A/fibroblast growth factor-2 expression, human umbilical vascular endothelial cell tube formation), and cell proliferation. Target interactions between circEIF6, miR-296-3p and MT2A were validated by luciferase/RNA immunoprecipitation assay. CircEIF6 was significantly upregulated in TNBC (P<0.05), correlating with advanced TNM (Tumor, Node, Metastasis) Classification of Malignant Tumors stage (P=0.01), tumor size (P=0.01) and poor prognosis. Silencing circEIF6 suppressed glycolysis, angiogenesis, and proliferation (P<0.05) by sponging miR-296-3p to downregulate MT2A. We conclude that circEIF6 promotes aerobic glycolysis and angiogenesis in TNBC via the miR-296-3p to target MT2A.