期刊
EMBO JOURNAL
卷 31, 期 8, 页码 1985-1998出版社
WILEY
DOI: 10.1038/emboj.2012.45
关键词
aerobic glycolysis; hexokinase 2; inflammation; microRNA-155; microRNA-143; the Warburg effect
资金
- Ministry of Science and Technology of China [2012CB910802, 2011CB811303, 2011CB966304]
- National Natural Science Foundation of China [90919016, 30970621, 31170754]
- Chinese Academy of Sciences [KSCX1-YW-R-64, KSCX2-YW-R-096]
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/EBP beta (a transcriptional activator for mir143), 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. The EMBO Journal (2012) 31, 1985-1998. doi:10.1038/emboj.2012.45; Published online 21 February 2012 Subject Categories: signal transduction; molecular biology of disease
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