Antitumor effect and biological pathways of a recombinant adeno-associated virus as a human renal cell carcinoma suppressor
详细信息 查看全文
- 作者：Jie Chen (1)
Xiyun Ruan (2)
Shaomei Wang (3)
Bin Zhang (3)
Bo Liu (4)
Zeqiang Sun (5)
Qingyong Liu (5) - 关键词：Renal cell carcinoma ; Recombinant adeno ; associated virus ; Von Hippel–Lindau ; Protein–protein interaction network ; Pathway enrichment analysis
- 刊名：Tumor Biology
- 出版年：2014
- 出版时间：November 2014
- 年：2014
- 卷：35
- 期：11
- 页码：10993-11003
- 全文大小：1,592 KB
- 参考文献：1. Nelson EC, Evans CP, Lara Jr PN. Renal cell carcinoma: current status and emerging therapies. Cancer Treat Rev. 2007;33:299-13. CrossRef
2. Coppin C, Le L, Porzsolt F, Wilt T Targeted therapy for advanced renal cell carcinoma. Cochrane Database Syst Rev. 2008;2
3. Van Spronsen D, De Weijer K, Mulders P, De Mulder P. Novel treatment strategies in clear-cell metastatic renal cell carcinoma. Anti-Cancer Drugs. 2005;16:709-7. CrossRef
4. Fukui N, Kageyama Y, Higashi Y, Kihara K, Kizaka-Kondoh S, Hiraoka M, et al. Development of a novel interferon-α2b gene construct with a repetitive hypoxia-inducible factor binding site and its suppressive effects on human renal cell carcinoma cell lines in vitro. Int J Clin Oncol. 2014;19:497-04. CrossRef
5. Board RE, Thistlethwaite FC, Hawkins RE. Anti-angiogenic therapy in the treatment of advanced renal cell cancer. Cancer Treat Rev. 2007;33:1-. CrossRef
6. Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013;369:722-1. CrossRef
7. Daya S, Berns KI. Gene therapy using adeno-associated virus vectors. Clin Microbiol Rev. 2008;21:583-3. CrossRef
8. Morris MR, Ricketts CJ, Gentle D, McRonald F, Carli N, Khalili H, et al. Genome-wide methylation analysis identifies epigenetically inactivated candidate tumour suppressor genes in renal cell carcinoma. Oncogene. 2011;30:1390-01. CrossRef
9. Varela I, Tarpey P, Raine K, Huang D, Ong CK, Stephens P, et al. Exome sequencing identifies frequent mutation of the swi/snf complex gene pbrm1 in renal carcinoma. Nature. 2011;469:539-2. CrossRef
10. Thompson M. Polybromo-1: the chromatin targeting subunit of the pbaf complex. Biochimie. 2009;91:309-9. CrossRef
11. Tang XJ, Ping BH, Pan CE, Yang GX, Wang QY. [Construction and identification of recombinant adeno-associated virus vector harboring fusion gene NT4-Ant-Shepherdin[79-87]]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2008;24:1143-.
12. Zheng Y, Zeng H, She H, Liu H, Sun N. Expression of peptide nap in rat retinal müller cells prevents hypoxia-induced retinal injuries and promotes retinal neurons growth. Biomed Pharmacother. 2010;64:417-3. CrossRef
13. Lisztwan J, Imbert G, Wirbelauer C, Gstaiger M, Krek W. The von Hippel–Lindau tumor suppressor protein is a component of an E3 ubiquitin–protein ligase activity. Genes Dev. 1999;13:1822-3. CrossRef
14. Na X, Duan HO, Messing EM, Schoen SR, Ryan CK, di Sant’Agnese PA, et al. Identification of the rna polymerase II subunit hsRPB7 as a novel target of the von Hippel–Lindau protein. EMBO J. 2003;22:4249-9. CrossRef
15. Pause A, Lee S, Worrell RA, Chen DY, Burgess WH, Linehan WM, et al. The von Hippel-Lindau tumor-suppressor gene product forms a stable complex with human CUL-2, a member of the Cdc53 family of proteins. Proc Natl Acad Sci. 1997;94:2156-1. CrossRef
16. Kim W, Kaelin Jr WG. The von Hippel–Lindau tumor suppressor protein: new insights into oxygen sensing and cancer. Curr Opin Gen Dev. 2003;13:55-0. CrossRef
17. George DJ, Kaelin WG. The von Hippel-Lindau protein, vascular endothelial growth factor, and kidney cancer. N Engl J Med. 2003;349:419-1. Zhang (3)
Bo Liu (4)
Zeqiang Sun (5)
Qingyong Liu (5)
1. Department of Urology, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, Shandong, China
2. Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China
3. Nephrology and Blood Purification Center, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, Shandong, China
4. ICU, Affiliated Hospital of Jining Medical University, Jining, 272129, Shandong, China
5. Department of Urology, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, 250014, Shandong, China - ISSN：1423-0380
文摘
The aims of this work are to study the antitumor effect of the adeno-associated virus on the xenografted tumors of chick embryo chorioallantoic membrane and predict potential genes and biological pathways which are associated with renal cell carcinoma. The adeno-associated virus NT4-TAT-6?×?His-VHLbeta was constructed and identified. Then, chick embryos with xenografted tumor were divided into three groups and respectively inoculated with rAAV/NT4-TAT-6?×?His-VHLbeta (group A), empty virus (group B), and phosphate-buffered saline (group C, the control subject). Antitumor effect in each group was investigated by means of immunofluorescence observation. Genes interacted with von Hippel–Lindau were screened by Search Tool for the Retrieval of Interacting Genes/Proteins database, while pathway analysis were performed based on Kyoto Encyclopedia of Genes and Genomes. The growth of xenografted tumors inoculated with recombinant adeno-associated virus was slower than the control subjects. The tumor volumes of group A showed significant difference compared with group B and group C (P--.05). Growth of xenografted tumors which administered with the recombinant adeno-associated virus was inhibited. Among the protein–protein interaction network, TCEB2, HIF1A, TCEB1, CUL2, RBX1, and PHF17 were hub genes which might be involved in the development of renal cell carcinoma. The most significant signaling pathway was renal cell carcinoma. In this paper, we constructed and identified the recombinant adeno-associated virus NT4-TAT-6?×?His-VHLbeta and studied the antitumor effect of the adeno-associated virus on xenografted tumors of chicken embryo chorioallantoic membrane. In addition, genes in the protein–protein interaction network which are associated with renal cell carcinoma were revealed and the biological pathway of renal cell carcinoma was identified. Our results provide a gene-therapeutic agent for the treatment of human renal cell carcinoma.