期刊
ONCOTARGET
卷 7, 期 16, 页码 22092-22102出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.8020
关键词
MiR-448; glucose metabolism; gastric cancer; lysine (K)-specific demethylase 2B; mitochondria respiration
资金
- National Natural Science Foundation of China [81172283]
- Natural Science Foundation of Fujian Province [2016J01619, 2012D037, 2015J01530, 2014CXB43]
MicroRNAs are critical in various human cancers, including gastric cancer (GC). However, the mechanism underlying the GC development remains elusive. In this study, we demonstrate that miR-448 is increased in GC samples and cell lines. Overexpression of miR-448 facilitated the proliferation of GC cells by stimulating glycolysis. Mechanistically, we identified KDM2B, a reader for methylated CpGs, as the target of miR-448 that represses glycolysis and promotes oxidative phosphorylation. Overexpression of miR-448 reduced both the mRNA and protein levels of KDM2B, whereas KDM2B re-expression abrogated the miR-448-mediated glycolytic activities. Furthermore, we discovered Myc as a key target of KDM2B that controls metabolic switch in GC. Importantly, a cohort of 81 GC tissues revealed that miR-448 level closely associated with a battery of glycolytic genes, in which KDM2B showed the strongest anti-correlation coefficient. In addition, enhanced miR-448 level was significantly associated with poor clinical outcomes of GC patients. Hence, we identified a previously unappreciated mechanism by which miR-448 orchestrate epigenetic, transcriptional and metabolic networks to promote GC progression, suggesting the possibility of therapeutic intervention against cancer metabolic pathways.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据