Ran Fang, Zhang Yanan, Shi Yajiao, Liu Jie, Li Huayue, Ding Lihua, Ye Qinong
Medical School of Guizhou University, Guiyang 550025, China.
Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing 100850, China.
J Oncol. 2021 Apr 19;2021:5529770. doi: 10.1155/2021/5529770. eCollection 2021.
Metabolic reprogramming of aerobic glycolysis is a hallmark of cancer cells. Regulators of aerobic glycolysis have become targets for cancer diagnosis and therapy. However, the regulators of aerobic glycolysis in breast cancer development have not been well elucidated. Here, we show that the phosphoglucomutase (PGM) family member PGM5 promotes conversion of glucose-1-phosphate (G1P) into glucose-6-phosphate (G6P) and inhibits breast cancer cell proliferation and migration through regulating aerobic glycolysis. In breast cancer patients, PGM5 is significantly downregulated, and its low expression is a predictor of poor prognosis. MicroRNA-1224-3p (miR-1224-3p) inhibits the PGM5 level through directly targeting its 3'-untranslated region and suppresses PGM5-mediated breast cancer cell proliferation, migration, and glycolytic function. Moreover, the miR-1224-3p/PGM5 axis regulates the expression of cell cycle- and apoptosis-related genes and the markers of epithelial-mesenchymal transition (EMT), a process involved in migration and metastasis of cancer cells. Taken together, our results indicate that miR-1224-3p/PGM5 axis plays important roles in breast cancer cell proliferation, migration, and aerobic glycolysis and may be a potential target for breast cancer therapy.
有氧糖酵解的代谢重编程是癌细胞的一个标志。有氧糖酵解的调节因子已成为癌症诊断和治疗的靶点。然而，乳腺癌发生过程中有氧糖酵解的调节因子尚未得到充分阐明。在此，我们表明磷酸葡萄糖变位酶（PGM）家族成员PGM5促进1-磷酸葡萄糖（G1P）转化为6-磷酸葡萄糖（G6P），并通过调节有氧糖酵解抑制乳腺癌细胞的增殖和迁移。在乳腺癌患者中，PGM5显著下调，其低表达是预后不良的一个预测指标。微小RNA-1224-3p（miR-1224-3p）通过直接靶向其3'-非翻译区抑制PGM5水平，并抑制PGM5介导的乳腺癌细胞增殖、迁移和糖酵解功能。此外，miR-1224-3p/PGM5轴调节细胞周期和凋亡相关基因的表达以及上皮-间质转化（EMT）的标志物，EMT是一个与癌细胞迁移和转移有关的过程。综上所述，我们的结果表明miR-1224-3p/PGM5轴在乳腺癌细胞增殖、迁移和有氧糖酵解中起重要作用，可能是乳腺癌治疗的一个潜在靶点。
