title: 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.
authors.affiliation: Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, China.|Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen, Fujian, China.
authors.forename: Xuehui
authors.initials: X
authors.lastname: Hong
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, China.
authors.forename: Xingfeng
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Yuekun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Radiation Oncology, Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey, USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Ding
authors.affiliation: Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, China.
authors.forename: Shifeng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Su
authors.affiliation: Department of Medical Imaging and Ultrasound, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, China.
authors.forename: Xinya
authors.initials: X
authors.lastname: Hong
authors.affiliation: Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, China.|Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen, Fujian, China.
authors.forename: Jianchun
authors.initials: J
authors.lastname: Cai
mesh_terms: D000818:Animals; D015536:Down-Regulation; D044783:F-Box Proteins / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006019:Glycolysis; D064593:Heterografts; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000096:biosynthesis*; D053208:Kaplan-Meier Estimate; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
chemical_list: D044783:F-Box Proteins; C557400:MIRN448 microRNA, human; D035683:MicroRNAs; D056484:Jumonji Domain-Containing Histone Demethylases; C534524:KDM2A protein, human
keywords: gastric cancer; glucose metabolism; lysine (K)-specific demethylase 2B; miR-448; mitochondria respiration