Zhang Zijian, Huang Shanzhou, Wang Huanyu, Wu Jian, Chen Dong, Peng Baogang, Zhou Qi
Department of Hepatic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.
Department of Thyroid and Breast Surgery, Nanshan District People's Hospital, Shenzhen, 518000, China.
Biochem Biophys Res Commun. 2016 Jun 10;474(4):673-679. doi: 10.1016/j.bbrc.2016.05.007. Epub 2016 May 4.
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™ 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/β-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. Downregulated HKDC1 expression repressed β-Catenin and c-Myc expression, which indicates that silencing HKDC1 may reduce proliferation and migration via inhibiting the Wnt/β-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.
快速进展和转移仍然是肝癌（HCC）主要的治疗失败模式。不幸的是，肝癌细胞增殖和迁移的潜在分子机制仍知之甚少。代谢异常在肿瘤发生和进展中起着关键作用。含己糖激酶结构域1（HKDC1）催化葡萄糖磷酸化。然而，HKDC1在癌症中的功能和机制尚不清楚。在本研究中，采用实时逆转录-聚合酶链反应（RT-PCR）和蛋白质免疫印迹法检测肝癌组织和细胞系中HKDC1的表达水平。应用Oncomine™癌症微阵列数据库分析HKDC1表达与肝癌临床特征之间的相关性。采用MTT法和Transwell迁移试验确定HKDC1在肝癌细胞中的功能。采用蛋白质免疫印迹法评估HKDC1对Wnt/β-连环蛋白信号通路的影响。在本研究中，我们发现与癌旁组织相比，肝癌组织中HKDC1表达水平升高。HKDC1高表达的肝癌患者总生存期（OS）较差。此外，较高的HKDC1水平还预示着孤立性、术前血清甲胎蛋白（AFP）水平升高和肿瘤直径较大的患者OS更差。此外，沉默HKDC1可抑制肝癌细胞在体外的增殖和迁移。HKDC1表达下调可抑制β-连环蛋白和c-Myc表达，这表明沉默HKDC1可能通过抑制肝癌中的Wnt/β-连环蛋白信号通路来减少增殖和迁移。总之，HKDC1为肝癌的肿瘤进展提供了进一步的见解，并可能为肝癌治疗提供一种新的预后生物标志物和治疗靶点。
