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PRR11 promotes ccRCC tumorigenesis by regulating E2F1 stability
Siming Chen, Zhiwen He, Tianchen Peng, Fenfang Zhou, Gang Wang, Kaiyu Qian, Lingao Ju, Yu Xiao, Xinghuan Wang
Siming Chen, Zhiwen He, Tianchen Peng, Fenfang Zhou, Gang Wang, Kaiyu Qian, Lingao Ju, Yu Xiao, Xinghuan Wang
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Research Article Cell biology Nephrology

PRR11 promotes ccRCC tumorigenesis by regulating E2F1 stability

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Abstract

Proline rich 11 (PRR11), a novel tumor-related gene, has been identified in different tumors. However, the relevant biological functions of PRR11 in human clear cell renal cell carcinoma (ccRCC) have not been studied. In this study, we first identified PRR11 as a biomarker of ccRCC and predictor of poor prognosis by bioinformatics. Then, we showed that PRR11 silencing substantially reduced ccRCC cell proliferation and migration in vitro and in vivo. Importantly, we found that PRR11 induced the degradation of the E2F1 protein through its interaction with E2F1, and PRR11 reduced the stability of the E2F1 protein in ccRCC cells, thereby affecting cell cycle progression. Further results indicated that the downregulation of E2F1 expression partially reversed the changes in ccRCC cell biology caused by PRR11 deletion. In addition, we showed that PRR11 was a target gene of c-Myc. The transcription factor c-Myc may have promoted the expression of PRR11 in ccRCC cells by binding to the PRR11 promoter region, thereby accelerating the progression of ccRCC. In summary, we found that PRR11 served as an oncogene in ccRCC, and PRR11 reduced the protein stability of E2F1 and could be activated by c-Myc.

Authors

Siming Chen, Zhiwen He, Tianchen Peng, Fenfang Zhou, Gang Wang, Kaiyu Qian, Lingao Ju, Yu Xiao, Xinghuan Wang

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Figure 1

PRR11 is an independent factor of ccRCC.

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PRR11 is an independent factor of ccRCC.
(A and B) The expression level ...
(A and B) The expression level of PRR11 in ccRCC cell lines (ACHN, 796-P, 786-O, and Caki-1 cells) and a human renal tubular epithelial cell line (HK2; n = 3). (C) PRR11 staining score of ccRCC tissues and adjacent tissues based on a tissue microarray (n = 89 ccRCC tissues and n = 89 adjacent tissues). (D) Correlation between the PRR11 staining score and the ccRCC pathological grade based on a tissue microarray (n = 32 for grade I, n = 31 for grade II, n = 25 for grade III, and n = 1 for grade IV). (E) Representative pattern of PRR11 protein expression in ccRCC tissues and adjacent tissues using tissue microarray sections. (F) Survival analysis of PRR11 expression based on a ccRCC tissue microarray. Scale bar: 400 μm (left) and 100 μm (right). The data are shown as mean ± SD. One-way ANOVA with Dunnett’s multiple comparisons test (A), 2-tailed t test (C), and 1-way ANOVA with Tukey’s multiple comparisons test (D) analyses were performed. *P < 0.05, **P < 0.01, ***P < 0.001. PRR11, proline rich 11; ccRCC, clear cell renal cell carcinoma.

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