EIF3D silencing suppresses renal cell carcinoma tumorigenesis via inducing G2/M arrest through downregulation of Cyclin B1/CDK1 signaling

Pan,Xiu-Wu; Chen,Lu; Hong,Yi; Xu,Dan-Feng; Liu,Xi; Li,Lin; Huang,Yi; Cui,Li-Ming; Gan,Si-Shun; Yang,Qi-Wei; Huang,Hai; Qu,Fa-Jun; Ye,Jian-Qing; Wang,Lin-Hui; Cui,Xin-Gang

doi:10.3892/ijo.2016.3459

EIF3D silencing suppresses renal cell carcinoma tumorigenesis via inducing G2/M arrest through downregulation of Cyclin B1/CDK1 signaling

Authors:
- Xiu-Wu Pan
- Lu Chen
- Yi Hong
- Dan-Feng Xu
- Xi Liu
- Lin Li
- Yi Huang
- Li-Ming Cui
- Si-Shun Gan
- Qi-Wei Yang
- Hai Huang
- Fa-Jun Qu
- Jian-Qing Ye
- Lin-Hui Wang
- Xin-Gang Cui
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Affiliations: Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China, Duruo Biotechnologies Inc., Shanghai 200233, P.R. China, Department of Urinary Surgery of Ruijin Hospital, Shanghai Jiaotong University, Shanghai 200025, P.R. China, Department of Urinary Surgery of Third Affiliated Hospital, Second Military Medical University, Shanghai 201805, P.R. China
Published online on: March 28, 2016 https://doi.org/10.3892/ijo.2016.3459
Pages: 2580-2590

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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.

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