Cullin7 的过表达与肝细胞癌的进展和发病机制有关。
Overexpression of Cullin7 is associated with hepatocellular carcinoma progression and pathogenesis.
机构信息
Department of Cardiothoracic Surgery, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Department of Pathology, Guangdong Provincial Key Laboratory of Liver Disease Research, the Third Affiliated Hospital, Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, Guangdong, 510630, China.
出版信息
BMC Cancer. 2017 Dec 6;17(1):828. doi: 10.1186/s12885-017-3839-7.
BACKGROUND
Overexpression of Cullin7 is associated with some types of malignancies. However, the part of Cullin7 in hepatocellular carcinoma remains unclear. The aim of this study was to investigate the role of Cullin7 in pathogenesis and the progression of hepatocellular carcinoma.
METHODS
In the present study, the expression of Cullin7 in hepatocellular carcinoma cell lines and five surgical hepatocellular carcinoma specimens was detected with quantitative reverse transcription PCR and western blotting. In addition, the protein expression of Cullin7 was examined in 162 cases of archived hepatocellular carcinoma using immunohistochemistry.
RESULTS
We found elevated expression of both mRNA and protein levels of Cullin7 in hepatocellular carcinoma cell lines, and Cullin7 protein was significantly upregulated in hepatocellular carcinoma compared with paired normal hepatic tissues. The immunohistochemistry analysis revealed that overexpression of Cullin7 occurred in 69.1% of hepatocellular carcinoma samples, which was a significantly higher rate than that in adjacent normal hepatic tissue (P < 0.01). Statistical analysis found that overexpression of Cullin7 was significantly associated with lymph node metastasis, tumor thrombus of the portal vein and advanced clinical stage (P < 0.05). Furthermore, by overexpressing Cullin7 in hepatocellular carcinoma HepG2 cells, we revealed that Cullin7 could significantly enhance cell proliferation, growth, migration and invasion. Conversely, knocking down Cullin7 expression with short hairpin RNAi in hepatocellular carcinoma HepG2 cells inhibited cell proliferation, growth, migration and invasion.
CONCLUSION
Our studies provide evidence that overexpression of Cullin7 plays an important role in the pathogenesis and progression of hepatocellular carcinoma and may be a valuable marker for hepatocellular carcinoma management.
背景
Cullin7 的过表达与某些类型的恶性肿瘤有关。然而，Cullin7 在肝细胞癌中的作用仍不清楚。本研究旨在探讨 Cullin7 在肝细胞癌发病机制和进展中的作用。
方法
本研究采用定量逆转录 PCR 和 Western blot 检测 Cullin7 在肝细胞癌细胞系和 5 例手术肝细胞癌标本中的表达。此外，采用免疫组织化学方法检测 162 例存档肝细胞癌组织中 Cullin7 的蛋白表达。
结果
我们发现 Cullin7 的 mRNA 和蛋白水平在肝细胞癌细胞系中均升高，与配对的正常肝组织相比，肝细胞癌中 Cullin7 蛋白明显上调。免疫组织化学分析显示，Cullin7 过表达发生在 69.1%的肝细胞癌样本中，明显高于相邻正常肝组织（P<0.01）。统计学分析发现，Cullin7 的过表达与淋巴结转移、门静脉癌栓和晚期临床分期显著相关（P<0.05）。此外，通过在肝细胞癌 HepG2 细胞中过表达 Cullin7，我们发现 Cullin7 可显著增强细胞增殖、生长、迁移和侵袭。相反，用短发夹 RNAi 敲低肝细胞癌 HepG2 细胞中的 Cullin7 表达可抑制细胞增殖、生长、迁移和侵袭。
结论
我们的研究结果表明，Cullin7 的过表达在肝细胞癌的发病机制和进展中起着重要作用，可能是肝细胞癌管理的一个有价值的标志物。
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