Upregulation of cleavage and polyadenylation specific factor 4 in lung adenocarcinoma and its critical role for cancer cell survival and proliferation.
Upregulation of cleavage and polyadenylation specific factor 4 in lung adenocarcinoma and its critical role for cancer cell survival and proliferation.
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肺腺癌中裂解和聚腺苷酸化特异性因子 4 的上调及其对癌细胞存活和增殖的关键作用
DOI：
10.1371/journal.pone.0082728
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Deng W
中科院分区：
文献类型：
--
作者：
Chen W;Guo W;Li M;Shi D;Tian Y;Li Z;Wang J;Fu L;Xiao X;Liu QQ;Wang S;Huang W;Deng W
裂解和多聚腺苷化特异因子4(CPSF4)是CPSF复合体中的一员，在mRNA多聚腺苷化和mRNA 3‘末端成熟过程中起着关键作用。然而，它在肺癌发病机制中的可能作用尚不清楚。在本研究中，我们研究了CPSF4在肺癌生长和生存中的生物学作用和临床意义，并阐明了其潜在的分子机制。我们发现CPSF4在肺腺癌细胞系和肿瘤组织中高表达，而在8个正常人体组织中检测不到。我们还发现，在肺腺癌患者中，CPSF4的过度表达与总体生存率较低相关(P<；0.001)。多因素生存分析显示，CPSF4的高表达是影响肺腺癌患者总体生存的独立预后因素。通过siRNA抑制CPSF4抑制肺癌细胞的增殖、集落形成和诱导凋亡。机制研究表明，这些作用是通过同时调节多个信号通路来实现的。SiRNA抑制CPSF4的表达可显著抑制PI3K、AKT、ERK1/2和JNK蛋白的磷酸化。相反，CPSF4的异位表达具有相反的作用。此外，CPSF4基因敲除还诱导了caspase-3和caspse-9蛋白的切割。综上所述，这些结果表明CPSF4在调节肺癌细胞的增殖和生存方面起着关键作用，可能成为肺腺癌的一个潜在的预后生物标志物和治疗靶点。
Cleavage and polyadenylation specific factor 4 (CPSF4), a member of CPSF complex, plays a key role in mRNA polyadenylation and mRNA 3′ ends maturation. However, its possible role in lung cancer pathogenesis is unknown. In this study, we investigated the biological role and clinical significance of CPSF4 in lung cancer growth and survival and elucidated its underlying molecular mechanisms. We found that CPSF4 was highly expressed in lung adenocarcinoma cell lines and tumor tissue but was undetectable in 8 normal human tissues. We also found that CPSF4 overexpression was correlated with poor overall survival in patients with lung adenocarcinomas (P<0.001). Multivariate survival analyses revealed that higher CPSF4 expression was an independent prognostic factor for overall survival of the patients with lung adenocarcinomas. Suppression of CPSF4 by siRNA inhibited lung cancer cells proliferation, colony formation, and induced apoptosis. Mechanism studies revealed that these effects were achieved through simultaneous modulation of multiple signaling pathways. Knockdown of CPSF4 expression by siRNA markedly inhibited the phosphorylation of PI3K, AKT and ERK1/2 and JNK proteins. In contrast, the ectopic expression of CPSF4 had the opposite effects. Moreover, CPSF4 knockdown also induced the cleavage of caspase-3 and caspse-9 proteins. Collectively, these results demonstrate that CPSF4 plays a critical role in regulating lung cancer cell proliferation and survival and may be a potential prognostic biomarker and therapeutic target for lung adenocarcinoma.
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影响因子：
16
作者：
Nemeroff, ME;Barabino, SML;Krug, RM
通讯作者：
Krug, RM
影响因子：
11.4
作者：
de Vries, H;Rüegsegger, U;Keller, W
通讯作者：
Keller, W
影响因子：
10.5
作者：
Barabino, SML;Hubner, W;Keller, W
通讯作者：
Keller, W
影响因子：
11.2
作者：
Ueda, Kentaro;Kawashima, Hiroyuki;Ji, Lin
通讯作者：
Ji, Lin
DOI：
10.1093/jnci/djn389
发表时间：
2008-12-03
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Jemal A;Thun MJ;Ries LA;Howe HL;Weir HK;Center MM;Ward E;Wu XC;Eheman C;Anderson R;Ajani UA;Kohler B;Edwards BK
通讯作者：
Edwards BK