MicroRNA-16-1-3p Represses Breast Tumor Growth and Metastasis by Inhibiting PGK1-Mediated Warburg Effect

作者：Tianxing Ye, Yingchun Liang, Deyu Zhang, Xuewu Zhang · 发表于：Frontiers in Cell and Developmental Biology · 年份：2020 · DOI：10.3389/fcell.2020.615154 · 被引用次数：65 · 研究领域：Cancer, Hypoxia, and Metabolism、MicroRNA in disease regulation、RNA modifications and cancer

The Warburg effect (aerobic glycolysis) is a hallmark of cancer and is becoming a promising target for diagnosis and therapy. Phosphoglycerate kinase 1 (PGK1) is the first adenosine triphosphate (ATP)-generating glycolytic enzyme in the aerobic glycolysis pathway and plays an important role in cancer development and progression. However, how microRNAs (miRNAs) regulate PGK1-mediated aerobic glycolysis remains unknown. Here, we show that miR-16-1-3p inhibits PGK1 expression by directly targeting its 3′-untranslated region. Through inhibition of PGK1, miR-16-1-3p suppressed aerobic glycolysis by decreasing glucose uptake, lactate and ATP production, and extracellular acidification rate, and increasing oxygen consumption rate in breast cancer cells. Aerobic glycolysis regulated by the miR-16-1-3p/PGK1 axis is critical for modulating breast cancer cell proliferation, migration, invasion and metastasis in vitro and in vivo . In breast cancer patients, miR-16-1-3p expression is negatively correlated with PGK1 expression and breast cancer lung metastasis. Our findings provide clues regarding the role of miR-16-1-3p as a tumor suppressor in breast cancer through PGK1 suppression. Targeting PGK1 through miR-16-1-3p could be a promising strategy for breast cancer therapy.