Glycolysis module activated by hypoxia-inducible factor 1α is related to the aggressive phenotype of hepatocellular carcinoma
Glycolysis module activated by hypoxia-inducible factor 1α is related to the aggressive phenotype of hepatocellular carcinoma
复制标题
DOI：
10.3892/ijo_00000058
复制
发表时间：
2008-10-01
影响因子：
5.2
通讯作者：
Oka, Masaaki
中科院分区：
文献类型：
--
作者：
Hamaguchi, Takashi;Iizuka, Norio;Oka, Masaaki
糖酵解水平的增加是肿瘤的细胞内标志，使癌细胞能够在各种条件下存活。为了阐明糖酵解增加在肝细胞癌（HCC）进展中的作用，我们使用汇总的转录组数据研究了60例HCC中14个糖酵解相关基因的表达模式与临床病理因素之间的关联。然后，我们评估了在HCC细胞中敲低由糖酵解相关基因编码的ENO 1的治疗效果。在这14个基因中，8个基因（GPI、ALDOA、TPI 1、GAPD、PGK、PGAM、ENO 1和PKM）的水平在伴有静脉浸润（VI）的HCC中显著高于无VI的HCC，所有这些基因都可以被缺氧诱导因子1 α（HIF-1 α）转录激活。我们的聚类分析显示，与这些基因表达水平没有增加的HCC患者相比，8个HIF-1 α调节基因激活的HCC患者的总生存期显著缩短（P=0.023）。通过实时逆转录PCR，在49例HCC的独立样本组中证实了ENO 1和VI水平之间的关联。在高糖和无糖条件下，小干扰RNA敲低ENO 1基因均能显著抑制HCC细胞系（HLE细胞）的增殖，并伴有S期细胞减少和G2/M期细胞增加。总的来说，这些数据表明HIF-1 α调节的糖酵解模块的激活与HCC的侵袭性表型密切相关，并且糖酵解模块基因ENO 1可能作为规避HCC转移的新靶点。
An increased level of glycolysis, an intracellular hallmark of neoplasms, enables cancer cells to survive under various conditions. To elucidate the role of increased glycolysis in the progression of hepatocellular carcinoma (HCC), we investigated the associations between the expression patterns of 14 glycolysis-related genes and clinicopathologic factors in 60 HCCs by using pooled transcriptome data. We then evaluated the therapeutic efficacy of the knockdown of ENO1,which is encoded by a glycolysis-related gene, in HCC cells. Among the 14 genes, levels of 8 genes (GPI, ALDOA, TPI1, GAPD, PGK, PGAM, ENO1 and PKM), all of which can be transcriptionally activated by hypoxia-inducible factor 1 alpha (HIF-1 alpha), were significantly higher in HCC with venous invasion (VI) than in HCC without VI. Our cluster analysis showed that HCC patients with activation of the 8 HIF-1 alpha-regulated genes had significantly shorter overall survival (P=0.023) than did HCC patients without increased expression levels of these genes. The association between the levels of ENO1 and VI was confirmed in an independent sample set of 49 HCCs by real-time reverse-transcription PCR. The knockdown of ENO1 by small-interfering RNA significantly inhibited the proliferation of an HCC cell line (HLE cells) in both the glucose-rich and glucose-free conditions, accompanied by a decreased S phase and increased G2/M phase of the cell cycle. Collectively, these data suggest that activation of an HIF-1 alpha-regulated glycolysis module is closely related to the aggressive phenotype of HCC, and that ENO1, a glycolysis module gene, might serve as a new target to circumvent HCC metastasis.