Key Laboratory of Systems Biomedicine, Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
J Cell Biochem. 2010 Dec 1;111(5):1244-51. doi: 10.1002/jcb.22851.
E2F3a is a transcription factor that has been shown to be overexpressed in liver cancer tissues. To characterize the function of E2F3a in hepatocellular carcinoma (HCC), effects of ectopic overexpression of E2F3a on cell cycle, apoptosis, and gene expression of HepG2 cells were studied. E2F3a significantly enhances the apoptotic rate of HepG2 cells by 33% but only has minor effects on cell proliferation. By using microarray analyses, we identified 162 target genes (160 upregulated and 2 downregulated) of the E2F3a. Differential expression of 11 genes was further confirmed by real-time PCR. Eight of these 11 genes, including XAF1, CEACAM1, STAT1, ATF3, TNFSF10, KLF6, CLDN1, and TAP1, were confirmed to be upregulated by more than twofold. Functional enrichments of differentially expressed genes retrieved 21 apoptosis-related genes and 32 transcriptional regulation-related genes. These results suggest that E2F3a induces apoptosis in HepG2 cells and plays important roles in regulating transcription. Finally, positive correlation was found between E2F3a and CEACAM1 mRNA levels in clinically well-differentiated human HCC specimens.
E2F3a 是一种转录因子,已被证明在肝癌组织中过度表达。为了研究 E2F3a 在肝细胞癌(HCC)中的功能,研究了异位过表达 E2F3a 对 HepG2 细胞周期、凋亡和基因表达的影响。E2F3a 显著增强了 HepG2 细胞的凋亡率 33%,但对细胞增殖只有轻微影响。通过微阵列分析,我们鉴定了 E2F3a 的 162 个靶基因(160 个上调和 2 个下调)。通过实时 PCR 进一步证实了 11 个基因的差异表达。这 11 个基因中的 8 个,包括 XAF1、CEACAM1、STAT1、ATF3、TNFSF10、KLF6、CLDN1 和 TAP1,被证实上调了两倍以上。差异表达基因的功能富集检索到 21 个与凋亡相关的基因和 32 个与转录调节相关的基因。这些结果表明,E2F3a 诱导 HepG2 细胞凋亡,并在调节转录中发挥重要作用。最后,在临床分化良好的人 HCC 标本中发现 E2F3a 与 CEACAM1 mRNA 水平之间存在正相关。