MicroRNA-143 (miR-143) Regulates Cancer Glycolysis via Targeting Hexokinase 2 Gene
MicroRNA-143 (miR-143) Regulates Cancer Glycolysis via Targeting Hexokinase 2 Gene
复制标题
MicroRNA-143 (miR-143) 通过靶向己糖激酶 2 基因调节癌症糖酵解
DOI：
10.1074/jbc.m112.373084
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发表时间：
2012-06-29
影响因子：
4.8
通讯作者：
Ji, Hongbin
中科院分区：
文献类型：
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作者：
Fang, Rong;Xiao, Tian;Ji, Hongbin
高糖酵解，众所周知的“瓦尔堡效应”，经常在各种癌症中观察到。miRNAs的失调是否导致了瓦尔堡效应仍然是未知的。由于miRNA在mRNA和蛋白质水平上调节基因表达，我们构建了一个基因功能关联网络，这使得我们能够检测基因活性而不是基因表达，从而综合分析基因表达和miRNA表达谱的微阵列数据，并识别癌症中糖酵解相关的基因-miRNA对。编码糖酵解第一限速酶的己糖激酶2（HK 2）是预测的并可能由包括miR-143在内的多种miRNA调控的基因之一。有趣的是，在人肺癌样品中，miR-143表达与HK 2蛋白水平而不是mRNA水平负相关。miR-143被哺乳动物雷帕霉素靶点激活下调，通过靶向HK 2降低葡萄糖代谢并抑制癌细胞增殖和肿瘤形成。总的来说，我们不仅建立了一种新的基因-miRNA对预测方法，而且还通过靶向HK 2将miR-143鉴定为癌症糖酵解的重要调节因子。
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.