High expression of hexokinase domain containing 1 is associated with poor prognosis and aggressive phenotype in hepatocarcinoma
High expression of hexokinase domain containing 1 is associated with poor prognosis and aggressive phenotype in hepatocarcinoma
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DOI：
10.1016/j.bbrc.2016.05.007
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发表时间：
2016-06-10
影响因子：
3.1
通讯作者：
Zhou, Qi
中科院分区：
文献类型：
--
作者：
Zhang, Zijian;Huang, Shanzhou;Zhou, Qi
快速进展和转移是肝癌治疗失败的主要原因。不幸的是，肝癌细胞增殖和迁移的潜在分子机制知之甚少。代谢异常在肿瘤的发生和发展中起关键作用。含己糖激酶结构域1（HKDC 1）催化葡萄糖的磷酸化。然而，HKDC 1在癌症中的功能和机制仍然未知。本研究采用实时荧光定量RT-PCR和Western blotting方法检测肝癌组织和细胞系中HKDC 1的表达水平。应用Oncomine（TM）癌症微阵列数据库分析HKDC 1表达与HCC临床特征的相关性。MTT法和Transwell迁移实验检测HKDC 1在肝癌细胞中的功能。采用Western blotting法检测HKDC 1对Wnt/β-catenin信号通路的影响。在这项研究中，我们发现HKDC 1的表达水平在肝癌组织中与癌旁组织相比有所升高。HKDC 1高表达的HCC患者的总生存率（OS）较差。HKDC 1水平越高，孤立患者的OS越差，术前血清甲胎蛋白（AFP）水平越高，肿瘤直径越大。此外，沉默HKDC 1抑制肝癌细胞的增殖和迁移在体外。下调HKDC 1表达可抑制beta-Catenin和c-Myc的表达，这表明沉默HKDC 1可能通过抑制Wnt/beta-catenin信号通路而降低HCC中的增殖和迁移。总之，HKDC 1提供了对HCC肿瘤进展的进一步了解，并可能为HCC治疗提供新的预后生物标志物和治疗靶点。(C)2016 Elsevier Inc. All rights reserved.
Rapid progress and metastasis remain the major treatment failure modes of hepatocarcinoma (HCC). Unfortunately, the underlying molecular mechanisms of hepatoma cell proliferation and migration are poorly understood. Metabolic abnormalities play critical roles in tumorigenesis and progression. Hexokinase domain containing 1 (HKDC1) catalyzes the phosphorylation of glucose. However, the functions and mechanisms of HKDC1 in cancer remain unknown. In this study, real-time RT-PCR and Western blotting assays were used to detect the HKDC1 expression levels in HCC tissues and cell lines. The Oncomine (TM) Cancer Microarray Database was applied to analysis the correlations between HKDC1 expression and HCC clinical characteristics. MTT and Transwell migration assays were performed to determine the functions of HKDC1 in HCC cells. The effect of HKDC1 on Wnt/beta-catenin signaling pathway was assessed using Western blotting assay. In this study, we found that HKDC1 expression levels were elevated in HCC tissues compared with the adjacent tissues. HCC patients with high expression levels of HKDC1 had poor overall survival (OS). Furthermore, higher HKDC1 levels also predicted a worse OS of patients within solitary, elevated pre-operated serum alpha fetoprotein (AFP) level and higher tumor diameter. Moreover, silencing HKDC1 suppressed HCC cells proliferation and migration in vitro. Down regulated HKDC1 expression repressed beta-Catenin and c-Myc expression, which indicates that silencing HKDC1 may reduce proliferation and migration via inhibiting the Wnt/beta-catenin signaling pathway in HCC. In summary, HKDC1 provides further insight into HCC tumor progression and may provide a novel prognostic biomarker and therapeutic target for HCC treatment. (C) 2016 Elsevier Inc. All rights reserved.