MiR-143, an Essential Regulator for Cancer Glycolysis
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Time: 2012-06-04
The “Warburg effect” describes the unique metabolic phenomenon that conversion of glucose into lactic acid is enhanced in cancer cells even in the presence of oxygen. Cancer cells preferentially utilize this far less efficient glycolytic process for energy production. Whether the deregulation of miRNAs contributes to the Warburg effect remains largely unknown. Since miRNA regulates target genes at both mRNA and protein levels, traditional methods simply using gene expression value for prediction gene-miRNA pairs deregulated in cancer may fail to pick up those genes mainly with protein level change.
Recently, a team of researchers led by Dr. JI Hongbin and Dr. LIU Xinyuan at Shanghai Institute of Biochemistry and Cell Biology, CAS, develop a new method by assigning a gene with an activity measure dependent on the expression level of its functional associated genes based on a previously constructed gene functional association network (gNET). FANG Rong, XIAO Tian, FANG Zhaoyuan and colleages integratively analyzed the miRNA and gene expression profiling in lung cancer and identified the gene-miRNA pairs significantly deregulated in cancer glycolysis. They found that, HK2, coding for the enzyme which catalyzes the first irreversible step of the glycolytic pathway, is one of the top 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, they 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. This work hopefully improves current understanding of the regulatory network of cancer metabolism and provide potential targets for the development of cancer therapeutic strategies.
This work entitled “miR-143 Regulates Cancer Glycolysis via Targeting Hexokinase 2” was published online in Journal of Biological Chemistry on May 16th, 2012, before its appearance in print.
This study was supported by grants from the Chinese Academy of Sciences, the Ministry of Science and Technology, National Natural Science Foundation of China, the Science and Technology Commission of Shanghai Municipality, Postdoctor Research Program of Shanghai Institutes for Biological Sciences and China Postdoctoral Science Foundation funded project.
AUTHOR CONTACT:
JI Hongbin
Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China
Figure legend: Schematic diagram shows linking mTOR signaling to the miRNAs that participate in the Warburg effect in cancer via regulating HK2.
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