Sun Meiqian, Mo Wenjuan, Fu Xuping, Wu Gang, Huang Yan, Tang Rong, Guo Yi, Qiu Minyan, Zhao Feng, Li Lin, Huang Shengdong, Mao Yumin, Li Yao, Xie Yi
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, PR China.
Front Biosci (Schol Ed). 2010 Jun 1;2(3):1127-44. doi: 10.2741/s122.
To investigate genetic mechanisms of hepatocarcinogenesis and identify potential anticancer targets in hepatocellular carcinoma (HCC), we analyzed microarray gene expression profiles between 33 HCCs and their corresponding noncancerous liver tissues. Functional analysis of differentially-expressed genes in HCC indicated that cell cycle dysregulation plays an important role in hepatocarcinogenesis. Based on 14 differentially-expressed genes involved in cell cycle in HCC, we applied Structural Equation Modeling (SEM) to establish a potential genetic network which could assist understanding of HCC molecular mechanisms. siRNA-mediated knock-down of two significantly up-regulated genes, minichromosome maintenance protein 2 (MCM2) and cyclin B1 (CCNB1), in HCC cells (SMMC-7721 and QGY-7703) induced G2/M-phase arrest, apoptosis and antiproliferation in HCC. Some up-regulated cell cycle-related genes in HCC were down-regulated following specific depletion of MCM2 or/and CCNB1 in HCC cells, which might well validate and complement the reconstructed cell cycle network. This study may contribute to further disclose hepatocarcinogenesis mechanism through systematically analyzed the HCC-related-cell-cycle pathway. This study also shows that MCM2 and CCNB1 could be promising prognostic and therapeutic targets for HCC.
为了研究肝癌发生的遗传机制并确定肝细胞癌（HCC）潜在的抗癌靶点，我们分析了33例肝癌及其相应癌旁肝组织之间的基因芯片表达谱。对肝癌中差异表达基因的功能分析表明，细胞周期失调在肝癌发生中起重要作用。基于肝癌中14个参与细胞周期的差异表达基因，我们应用结构方程模型（SEM）建立了一个潜在的遗传网络，以帮助理解肝癌的分子机制。在肝癌细胞（SMMC - 7721和QGY - 7703）中，siRNA介导的两个显著上调基因，微小染色体维持蛋白2（MCM2）和细胞周期蛋白B1（CCNB1）的敲低诱导了肝癌细胞的G2/M期阻滞、凋亡和增殖抑制。在肝癌细胞中特异性敲低MCM2或/和CCNB1后，肝癌中一些上调的细胞周期相关基因被下调，这可能很好地验证和补充了重建的细胞周期网络。本研究可能有助于通过系统分析肝癌相关细胞周期途径进一步揭示肝癌发生机制。本研究还表明，MCM2和CCNB1可能是肝癌有前景的预后和治疗靶点。
