title: Antitumor effect and biological pathways of a recombinant adeno-associated virus as a human renal cell carcinoma suppressor.
abstract: 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 < 0.05). 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.
authors.affiliation: Department of Urology, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, Shandong, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Xiyun
authors.initials: X
authors.lastname: Ruan
authors.forename: Shaomei
authors.initials: S
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Zeqiang
authors.initials: Z
authors.lastname: Sun
authors.forename: Qingyong
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D036022:Capsid Proteins / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D049109:Cell Proliferation; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000378:metabolism / Q000473:pathology; D000229:Dependovirus / Q000235:genetics*; D015696:Gene Products, tat / Q000235:genetics; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000627:therapeutic use*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D060066:Protein Interaction Maps; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047368:Tumor Burden; D014407:Tumor Cells, Cultured; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D036022:Capsid Proteins; D015696:Gene Products, tat; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human
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