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.
Highlights
Renal cell carcinoma (RCC), a tumor associated with high morbidity and mortality, seriously endangers the lives and health of people worldwide
Based on The Cancer Genome Atlas (TCGA) database (539 Clear cell RCC (ccRCC) tissues and 72 normal kidney tissues), we showed that Proline rich 11 (PRR11) was highly expressed in patients with ccRCC (Supplemental Figure 1, B and C)
The lack of endogenous PRR11 expression led to slower degradation of endogenous E2F1 (Figure 7, F–K). These results indicate that PRR11 interacted with the E2F1 to attenuate the stability of E2F1 protein in order to affect the progression of the cell cycle and promote the development of ccRCC
Summary
Renal cell carcinoma (RCC), a tumor associated with high morbidity and mortality, seriously endangers the lives and health of people worldwide. One domain is the zinc finger domain, which can bind to DNA to regulate transcription, and the other domain is the proline-rich domain, which can bind to other domains and mediate protein-protein interactions, affecting the occurrence of tumors [13,14,15,16,17]. Consistent with these results of functional domain analysis, we found that PRR11 could interact with E2F1 and reduce its protein stability, affecting the occurrence and development of ccRCC tumors
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