The miR-15b-5p/PDK4 axis regulates osteosarcoma proliferation through modulation of the Warburg effect

被引:44
作者
Weng, Yiping [1 ]
Shen, Yifei [1 ]
He, Yunjie [2 ]
Pan, Xiaohui [1 ]
Xu, Jingwen [3 ]
Jiang, Yuqing [1 ]
Zhang, Qiang [1 ]
Wang, Shenyu [1 ]
Kong, Fanqi [4 ]
Zhao, Shujie [4 ]
Zhou, Dong [1 ]
Zhang, Yunkun [1 ]
机构
[1] Nanjing Med Univ, Affiliated Hosp, Dept Orthoped, Changzhou Peoples Hosp 2, Changzhou 213003, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Affiliated Hosp 1, Clin Sch 1, Nanjing 210029, Jiangsu, Peoples R China
[3] Nanjing Med Univ, Affiliated Hosp, Dept Nutr, Changzhou Peoples Hosp 2, Changzhou 213003, Jiangsu, Peoples R China
[4] Nanjing Med Univ, Dept Orthoped, Affiliated Hosp 1, Nanjing 210000, Jiangsu, Peoples R China
关键词
miR-15b-5p; Osteosarcoma; PDK4; Proliferation; Warburg effect; CANCER CELLS; PYRUVATE-DEHYDROGENASE; MULTIDRUG-RESISTANCE; METABOLIC PLASTICITY; THERAPEUTIC TARGET; MIR-15B; METASTASIS; EXPRESSION;
D O I
10.1016/j.bbrc.2018.08.035
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Blocking aerobic glycolysis has been proposed as an attractive therapeutic strategy for impairing the proliferation of cancer cells. However, the underlying mechanisms are poorly understood. Here, we show that miR-15b-5p was downregulated in osteosarcoma (OS) and that lower expression of miR-15b-5p promoted proliferation and contributed to the Warburg effect in OS cells. Mechanistically, miR-15b-5p acted as a tumor suppressor in OS by directly targeting pyruvate dehydrogenase kinase-4 and inhibiting its expression. These results reveal a previously unknown function of miR-15b-5p in OS, which is associated with metabolic alterations that promote cancer progression. miR-15b-5p may play an essential role in the molecular therapy of patients with OS. (C) 2018 Elsevier Inc. All rights reserved.
引用
收藏
页码:2749 / 2757
页数:9
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