title: EIF3D silencing suppresses renal cell carcinoma tumorigenesis via inducing G2/M arrest through downregulation of Cyclin B1/CDK1 signaling.
abstract: There are no effective therapies for advanced renal cell carcinoma (RCC), except for VEGFR inhibitors with only ~50% response rate. To identify novel targets and biomarkers for RCC is of great importance in treating RCC. In this study, we observed that eukaryotic initiation factor 3d (EIF3D) expression was significantly increased in RCC compared with paracarcinoma tissue using immunohistochemistry staining and western blot analysis. Furthermore, bioinformatics meta-analysis using ONCOMINE microarray datasets showed that EIF3D mRNA expressions in CCRCC tissue specimens were significantly higher than that in normal tissue specimens. In addition, RCC tissue microarray demonstrated that elevated EIF3D expression was positively correlated with TNM stage and tumor size. EIF3D silencing in human 786-O and ACHN CCRCC cell lines by RNA interference demonstrated that EIF3D knockdown obviously inhibited cell proliferation and colony formation, caused G2/M arrest through downregulation of Cyclin B1 and Cdk1 and upregulation of p21, and induced apoptosis shown by sub-G1 accumulation and RARP cleavage. Moreover, correlation analysis using ONCOMINE microarray datasets indicated that increased EIF3D mRNA expression was positively correlated to PCNA, Cyclin B1 and CDK1 mRNA expression in RCC. Collectively, these results provide reasonable evidences that EIF3D may function as a potential proto-oncogene that participates in the occurrence and progression of RCC.
authors.affiliation: Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Xiu-Wu
authors.initials: XW
authors.lastname: Pan
authors.affiliation: Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Duruo Biotechnologies Inc., Shanghai 200233, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Department of Urinary Surgery of Ruijin Hospital, Shanghai Jiaotong University, Shanghai 200025, P.R. China.
authors.forename: Dan-Feng
authors.initials: DF
authors.lastname: Xu
authors.affiliation: Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Urinary Surgery of Ruijin Hospital, Shanghai Jiaotong University, Shanghai 200025, P.R. China.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Cui
authors.affiliation: Department of Urinary Surgery of Third Affiliated Hospital, Second Military Medical University, Shanghai 201805, P.R. China.
authors.forename: Si-Shun
authors.initials: SS
authors.lastname: Gan
authors.affiliation: Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Qi-Wei
authors.initials: QW
authors.lastname: Yang
authors.affiliation: Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Hai
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Urinary Surgery of Third Affiliated Hospital, Second Military Medical University, Shanghai 201805, P.R. China.
authors.forename: Fa-Jun
authors.initials: FJ
authors.lastname: Qu
authors.affiliation: Department of Urinary Surgery of Third Affiliated Hospital, Second Military Medical University, Shanghai 201805, P.R. China.
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Ye
authors.affiliation: Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Lin-Hui
authors.initials: LH
authors.lastname: Wang
authors.affiliation: Department of Urinary Surgery of Third Affiliated Hospital, Second Military Medical University, Shanghai 201805, P.R. China.
authors.forename: Xin-Gang
authors.initials: XG
authors.lastname: Cui
mesh_terms: D016203:CDC2 Protein Kinase; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D039621:Eukaryotic Initiation Factor-3 / Q000235:genetics* / Q000378:metabolism*; D059565:G2 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009367:Neoplasm Staging; D000090063:Proto-Oncogene Mas; D034622:RNA Interference; D015398:Signal Transduction
chemical_list: C534699:CCNB1 protein, human; D056744:Cyclin B1; C000609002:EIF3D protein, human; D039621:Eukaryotic Initiation Factor-3; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases