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MiR-448 promotes glycolytic metabolism of gastric cancer by downregulating KDM2B.


ABSTRACT: 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.

SUBMITTER: Hong X 

PROVIDER: S-EPMC5008346 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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MiR-448 promotes glycolytic metabolism of gastric cancer by downregulating KDM2B.

Hong Xuehui X   Xu Yang Y   Qiu Xingfeng X   Zhu Yuekun Y   Feng Xing X   Ding Zhijie Z   Zhang Shifeng S   Zhong Lifeng L   Zhuang Yifan Y   Su Chen C   Hong Xinya X   Cai Jianchun J  

Oncotarget 20160401 16


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. Overexpres  ...[more]

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