title: MicroRNA-143 (miR-143) regulates cancer glycolysis via targeting hexokinase 2 gene.
abstract: High glycolysis, well known as "Warburg effect," is frequently observed in a variety of cancers. Whether the deregulation of miRNAs contributes to the Warburg effect remains largely unknown. Because miRNA regulates gene expression at both mRNA and protein levels, we constructed a gene functional association network, which allows us to detect the gene activity instead of gene expression, to integratively analyze the microarray data for gene expression and miRNA expression profiling and identify glycolysis-related gene-miRNA pairs deregulated in cancer. Hexokinase 2 (HK2), coding for the first rate-limiting enzyme of glycolysis, is among the top list of genes predicted and potentially regulated by multiple miRNAs including miR-143. Interestingly, miR-143 expression was inversely associated with HK2 protein level but not mRNA level in human lung cancer samples. miR-143, down-regulated by mammalian target of rapamycin activation, reduces glucose metabolism and inhibits cancer cell proliferation and tumor formation through targeting HK2. Collectively, we have not only established a novel methodology for gene-miRNA pair prediction but also identified miR-143 as an essential regulator of cancer glycolysis via targeting HK2.
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Fang
authors.forename: Tian
authors.initials: T
authors.lastname: Xiao
authors.forename: Zhaoyuan
authors.initials: Z
authors.lastname: Fang
authors.forename: Yihua
authors.initials: Y
authors.lastname: Sun
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Yijun
authors.initials: Y
authors.lastname: Gao
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Liu
authors.forename: Haiquan
authors.initials: H
authors.lastname: Chen
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Liu
authors.forename: Hongbin
authors.initials: H
authors.lastname: Ji
mesh_terms: D000465:Algorithms; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D002455:Cell Division / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis / Q000502:physiology; D057809:HEK293 Cells; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D008957:Models, Genetic; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: C542359:MIRN143 microRNA, human; D035683:MicroRNAs; C532884:MIRN143 microRNA, mouse; D006593:Hexokinase; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases