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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 5

Reduction in PRR11 expression attenuated the in vivo proliferation and migration of ccRCC cells.

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Reduction in PRR11 expression attenuated the in vivo proliferation and m...
(A and B) The knockdown effect of LV-shPRR11 in ACHN cells was verified at the mRNA and protein levels (n = 3). (C) LV-NC and LV-shPRR11 cells were subcutaneously injected into nude mice to establish xenograft models. After 7 weeks, the xenografts were removed and photographed (n = 8). (D and E) The tumor volumes and weights were analyzed and evaluated (n = 8). (F) H&E staining was used to determine the degree of tumor malignancy, and IHC staining was used to evaluate the expression of PRR11 and Ki67 (n =8). Scale bar: 200 μm. (G and H) Quantification of the percentage of Ki67-positive cells and the PRR11 staining score (n = 8). (I–K) We established a lung metastasis model, detected the fluorescence intensity of the lung tumors, and performed H&E staining (n = 6). Scale bar: 100 μm. The data are shown as mean ± SD. Two-tailed t test analyses were performed. *P < 0.05, **P < 0.01, ***P < 0.001. PRR11, proline rich 11; ccRCC, clear cell renal cell carcinoma; LV-NC, lentiviral control shRNA.

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ISSN 2379-3708

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