Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiaotong University, Shanghai, China.
J Cell Biochem. 2018 Apr;119(4):3429-3439. doi: 10.1002/jcb.26513. Epub 2017 Dec 26.
E2F3 is a transcription factor that has been shown to be overexpressed in hepatocellular carcinoma (HCC). It is well-known that the E2F3 gene encodes two proteins E2F3a and E2F3b. Therefore, the functions of the two distinct isoforms need to be clarified separately. To characterize the function of E2F3b in HCC, the effects of ectopic expression of E2F3b on cell proliferation, cell cycle, apoptosis and gene expression were investigated. E2F3b promoted G1/S phase transition and markedly increased cell proliferation, but had minor effect on apoptosis. Microarray analyses identified 366 differentially expressed genes (171 upregulated and 195 downregulated) in E2F3b- overexpressing cells. Differential expression of 16 genes relevant to cell cycle and cell proliferation were further verified by real-time PCR. Six genes, including CDC2, CCNE1, ARF, MAP4K2, MUSK, and PAX2 were confirmed to be upregulated by more than twofold; one gene, CCNA2 was validated to be downregulated by more than twofold. We also confirmed that E2F3b increased the protein levels of both cyclin E and Arf but did not affect cyclin D1 protein. These results suggest that E2F3b functions as an important promoter for cell proliferation and plays important roles in transcriptional regulation in HepG2 liver cancer cells.
E2F3 是一种转录因子，已被证明在肝细胞癌 (HCC) 中过表达。众所周知，E2F3 基因编码两种蛋白质 E2F3a 和 E2F3b。因此，需要分别阐明这两种不同异构体的功能。为了研究 E2F3b 在 HCC 中的功能，研究了异位表达 E2F3b 对细胞增殖、细胞周期、凋亡和基因表达的影响。E2F3b 促进 G1/S 期过渡，显著增加细胞增殖，但对凋亡的影响较小。微阵列分析确定了 E2F3b 过表达细胞中 366 个差异表达基因（171 个上调和 195 个下调）。通过实时 PCR 进一步验证了与细胞周期和细胞增殖相关的 16 个基因的差异表达。六个基因，包括 CDC2、CCNE1、ARF、MAP4K2、MUSK 和 PAX2，被证实上调超过两倍；一个基因，CCNA2，被证实下调超过两倍。我们还证实，E2F3b 增加了细胞周期蛋白 E 和 Arf 的蛋白水平，但不影响细胞周期蛋白 D1 蛋白。这些结果表明，E2F3b 作为细胞增殖的重要启动子发挥作用，并在 HepG2 肝癌细胞中转录调节中发挥重要作用。
