HomeoboxC6通过诱导上皮细胞-间充质转化促进肝癌肺转移

HomeoboxC6 promotes lung metastasis of liver cancer by inducing EMT

目的肺转移癌的发生严重影响着肿瘤患者手术预后。找到肺转移癌发生的分子途径，将有利于减少肺转移癌的发生，改善肿瘤患者预后效果。同源异型盒C6（HOXC6）属于转录因子蛋白家族，在胚胎发育的形态发生和分化过程中起关键作用。据报道，HOXC6在多种肿瘤中高表达，且参与了肿瘤的进展。本研究以肝癌患者为研究对象，通过临床病例随访结合体外细胞实验，探讨HOXC6在肝癌肺转移过程中的具体分子机制。方法收集肝癌手术患者组织标本及术后临床病理资料进行统计学分析，并应用细胞培养、质粒转染、RT-PCR及Westernblot检测肿瘤细胞中HOXC6表达对上皮细胞-间充质转化（EMT）机制的影响及肿瘤细胞活性的影响。结果与对照组比较，HOXC6过表达的肝癌患者术后发生肺转移的人数明显增多（χ2=4744，P=0．029），HOXC6过表达的肝癌细胞中间充质细胞表型的细胞标记物表达水平明显升高（N—Cadherin：t=6．543，P=0．000，Vimentin：t=1．325，P=0.000），而上皮细胞表型细胞标志物表达水平明显降低（t=11．547，P=0．000），EMT相关转录因子表达水平也明显增高（Twist1：t=5．774，P=0．000，Snail：t=3．849，P=0．000）。结论HOXC6可通过诱导EMT促进肝癌肺转移。

Objective The lung metastasis is a serious influence on the prognosis of tumor patients. Finding the molecular pathway of pulmonary metastasis could help to reduce the occurrence and improve prognosis. HomeoboxC6（HOXC6） belongs to a transcription factor protein family,which plays a key role in the morphogenesis and differentiation of embryonic development. It is reported that HOXC6 is highly expressed in various tumors and involved in tumor progression. In this research, we study on patients with hepatocellular carcinoma,investigate the molecular mechanism of HOXC6 in lung metastasis of hepatocellular carcinoma by clinical cases follow-up and in vitro cell experiments. Methods The tissue specimen and pathological data of postoperative hepatocellular carcinoma patients were collected and analyzed. The effect of HOXC6 expression on EMT and activity of tumor cells was detected by cell culture,plasmid transfection,RT-PCR and Western blot. Results Compared with the control group, the number of lung metastasis in HCC patients with HOXC6 overexpression was significantly increased （ χ2= 4. 744, P = 0.029）, mesenchymal markers was significantly elevated in HOXC6 overexpressed hepatoeellular carcinoma cells （N-Cadherin： t = 6. 543, P = 0. 000, Vimentin ： t = 1. 325, P = 0. 000）, and epithelial markers was significantly decreased （t = 11.547, P = 0.000）, level of EMT related transcription factors was also increased obviously （Twist 1： t = 5. 774, P = 0. 000, Snail： t = 3. 849, P0. 000）. Conclusions HOXC6 can promote lung metastasis of hepatocellular carcinoma by inducing EMT.