Characterization of E2F3a Function in HepG2 Liver Cancer Cells
Characterization of E2F3a Function in HepG2 Liver Cancer Cells
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DOI：
10.1002/jcb.22851
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发表时间：
2010-12-01
影响因子：
4
通讯作者：
Wu, Qiang
中科院分区：
文献类型：
--
作者：
Li, Wei;Ni, Guo-Xin;Wu, Qiang
E2 F3 a是一种转录因子，已被证明在肝癌组织中过表达。为探讨E2 F3 a在肝细胞癌（HCC）中的作用，研究E2 F3 a异位过表达对HepG 2细胞周期、凋亡及基因表达的影响。E2 F3 a使FlepG 2细胞的凋亡率显著增加33%，但对细胞增殖的影响很小。通过基因芯片分析，我们鉴定了162个E2 F3 a靶基因（160个上调和2个下调）。11个基因的差异表达通过实时荧光定量PCR进一步证实。在这11个基因中，有8个基因，包括XAF 1、CEACAM 1、STAT 1、ATF 3、TNFSF 10、KLF 6、CLDN 1和TAP 1，被证实上调了2倍以上。差异表达基因的功能富集共获得21个糖尿病相关基因和32个转录调控相关基因。这些结果表明，E2 F3 a诱导HepG 2细胞凋亡，并在转录调控中发挥重要作用。最后，在临床分化良好的人HCC标本中发现E2 F3 a和CEACAM 1 mRNA水平之间呈正相关。J.细胞。111：1244-1251，2010. (C)2010 Wiley-Liss，Inc.
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 FlepG2 cells by 33% but only has minor effects on cell proliferation. By using microarray analyses, we identified 162 target genes (160 upregulatcd 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 upregulatcd 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. J. Cell. Biochem. 111: 1244-1251, 2010. (C) 2010 Wiley-Liss, Inc.