CPSF4 activates telomerase reverse transcriptase and predicts poor prognosis in human lung adenocarcinomas
作者： Wangbing Chen , Lijun Qin , Shusen Wang , Mei Li , Dingbo Shi
DOI: 10.1016/J.MOLONC.2014.02.001
关键词:
摘要: The elevated expression and activation of human telomerase reverse transcriptase (hTERT) is associated with the unlimited proliferation cancer cells. However, excise mechanism hTERT regulation during carcinogenesis not well understood. In this study, we discovered cleavage polyadenylation specific factor 4 (CPSF4) as a novel tumorspecific promoter-regulating protein in lung cells identified roles CPSF4 regulating growth. ectopic overexpression upregulated promoter-driven report gene activated endogenous mRNA activity normal contrast, knockdown by siRNA had opposite effects. also significantly inhibited tumor cell growth vitro xenograft mouse model vivo, inhibitory effect was partially mediated decreasing hTERT. High both proteins were detected adenocarcinoma comparison Tissue microarray immunohistochemical analysis adenocarcinomas revealed strong positive correlation between proteins. Moreover, KaplaneMeier showed that patients high levels shorter overall survival than those low levels. Collectively, these results demonstrate plays critical role tumorigenesis may be new prognosis adenocarcinomas. 2014 Federation European Biochemical Societies.
utsystem.edu参考文章(50)
Wu-Guo Deng, Kenneth K. Wu, Regulation of Inducible Nitric Oxide Synthase Expression by p300 and p50 Acetylation Journal of Immunology. ,vol. 171, pp. 6581- 6588 ,(2003) , 10.4049/JIMMUNOL.171.12.6581
Naomi Goldfinger, Ari Meerson, Varda Rotter, Igor Shats, Michael Milyavsky, Shai Senderovich, Neta Erez, Doron Ginsberg, Xiaohu Tang, Yuval Tabach, Curtis C. Harris, Prolonged Culture of Telomerase-Immortalized Human Fibroblasts Leads to a Premalignant Phenotype Cancer Research. ,vol. 63, pp. 7147- 7157 ,(2003)
JUN‐PING LIU, Studies of the molecular mechanisms in the regulation of telomerase activity The FASEB Journal. ,vol. 13, pp. 2091- 2104 ,(1999) , 10.1096/FASEBJ.13.15.2091
Scott L. Weinrich, Ron Pruzan, Libin Ma, Michel Ouellette, Valeric M. Tesmer, Shawn E. Holt, Andrea G. Bodnar, Serge Lichtsteiner, Nam W. Kim, James B. Trager, Rebecca D. Taylor, Ruben Carlos, William H. Andrews, Woodring E. Wright, Jerry W. Shay, Calvin B. Harley, Gregg B. Morin, Reconstitution of human telomerase with the template RNA component hTR and the catalytic protein subunit hTRT Nature Genetics. ,vol. 17, pp. 498- 502 ,(1997) , 10.1038/NG1297-498
MU-HAN LÜ, ZHONG-LI LIAO, XIAO-YAN ZHAO, YA-HAN FAN, XIAN-LONG LIN, DIAN-CHUN FANG, HONG GUO, SHI-MING YANG, hTERT-based therapy: a universal anticancer approach (Review). Oncology Reports. ,vol. 28, pp. 1945- 1952 ,(2012) , 10.3892/OR.2012.2036
Xiaoping Tian, Bo Chen, Xiaochuan Liu, Telomere and Telomerase as Targets for Cancer Therapy Applied Biochemistry and Biotechnology. ,vol. 160, pp. 1460- 1472 ,(2010) , 10.1007/S12010-009-8633-9
Martin E. Nemeroff, Silvia M.L. Barabino, Yongzhong Li, Walter Keller, Robert M. Krug, Influenza Virus NS1 Protein Interacts with the Cellular 30 kDa Subunit of CPSF and Inhibits 3′ End Formation of Cellular Pre-mRNAs Molecular Cell. ,vol. 1, pp. 991- 1000 ,(1998) , 10.1016/S1097-2765(00)80099-4
Wu-Guo Deng, Ying Zhu, Kenneth K. Wu, Role of p300 and PCAF in regulating cyclooxygenase-2 promoter activation by inflammatory mediators. Blood. ,vol. 103, pp. 2135- 2142 ,(2004) , 10.1182/BLOOD-2003-09-3131
Frida E. Kleiman, James L. Manley, The BARD1-CstF-50 interaction links mRNA 3' end formation to DNA damage and tumor suppression. Cell. ,vol. 104, pp. 743- 753 ,(2001) , 10.1016/S0092-8674(01)00270-7
S. B. Cohen, M. E. Graham, G. O. Lovrecz, N. Bache, P. J. Robinson, R. R. Reddel, Protein Composition of Catalytically Active Human Telomerase from Immortal Cells Science. ,vol. 315, pp. 1850- 1853 ,(2007) , 10.1126/SCIENCE.1138596