title: A novel miR-155/miR-143 cascade controls glycolysis by regulating hexokinase 2 in breast cancer cells.
abstract: Cancer cells preferentially metabolize glucose through aerobic glycolysis. This phenomenon, known as the Warburg effect, is an anomalous characteristic of glucose metabolism in cancer cells. Chronic inflammation is a key promoting factor of tumourigenesis. It remains, however, largely unexplored whether and how pro-tumourigenic inflammation regulates glucose metabolism in cancer cells. Here, we show that pro-inflammatory cytokines promote glycolysis in breast cancer cells, and that the inflammation-induced miR-155 functions as an important mediator in this process. We further show that miR-155 acts to upregulate hexokinase 2 (hk2), through two distinct mechanisms. First, miR-155 promotes hk2 transcription by activation of signal transducer and activator of transcription 3 (STAT3), a transcriptional activator for hk2. Second, via targeting C/EBPβ (a transcriptional activator for mir-143), miR-155 represses mir-143, a negative regulator of hk2, thus resulting in upregulation of hk2 expression at the post-transcriptional level. The miR-155-mediated hk2 upregulation also appears to operate in other types of cancer cells examined. We suggest that the miR-155/miR-143/HK2 axis may represent a common mechanism linking inflammation to the altered metabolism in cancer cells.
authors.affiliation: State Key Laboratory of Molecular Biology, Graduate School of Chinese Academy of Sciences, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Jiang
authors.forename: Ling-Fei
authors.initials: LF
authors.lastname: Zhang
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Zhang
authors.forename: Song
authors.initials: S
authors.lastname: Hu
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Lu
authors.forename: Sheng
authors.initials: S
authors.lastname: Liang
authors.forename: Biao
authors.initials: B
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Dangsheng
authors.initials: D
authors.lastname: Li
authors.forename: En-Duo
authors.initials: ED
authors.lastname: Wang
authors.forename: Mo-Fang
authors.initials: MF
authors.lastname: Liu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000503:physiopathology; D045744:Cell Line, Tumor; D006019:Glycolysis; D006593:Hexokinase / Q000096:biosynthesis*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D006593:Hexokinase