PRR11 promotes ccRCC tumorigenesis by regulating E2F1 stability
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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Clinical investigation
2021-10-01
|
| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.145172 |
| _version_ | 1818549300755431424 |
|---|---|
| author | Siming Chen Zhiwen He Tianchen Peng Fenfang Zhou Gang Wang Kaiyu Qian Lingao Ju Yu Xiao Xinghuan Wang |
| author_facet | Siming Chen Zhiwen He Tianchen Peng Fenfang Zhou Gang Wang Kaiyu Qian Lingao Ju Yu Xiao Xinghuan Wang |
| author_sort | Siming Chen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T08:31:34Z |
| format | Article |
| id | doaj.art-6890ec4f4bd240a8a8727a98c3d6249b |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-12-12T08:31:34Z |
| publishDate | 2021-10-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-6890ec4f4bd240a8a8727a98c3d6249b2022-12-22T00:31:05ZengAmerican Society for Clinical investigationJCI Insight2379-37082021-10-01619PRR11 promotes ccRCC tumorigenesis by regulating E2F1 stabilitySiming ChenZhiwen HeTianchen PengFenfang ZhouGang WangKaiyu QianLingao JuYu XiaoXinghuan WangProline 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.https://doi.org/10.1172/jci.insight.145172Cell biologyNephrology |
| spellingShingle | Siming Chen Zhiwen He Tianchen Peng Fenfang Zhou Gang Wang Kaiyu Qian Lingao Ju Yu Xiao Xinghuan Wang PRR11 promotes ccRCC tumorigenesis by regulating E2F1 stability JCI Insight Cell biology Nephrology |
| title | PRR11 promotes ccRCC tumorigenesis by regulating E2F1 stability |
| title_full | PRR11 promotes ccRCC tumorigenesis by regulating E2F1 stability |
| title_fullStr | PRR11 promotes ccRCC tumorigenesis by regulating E2F1 stability |
| title_full_unstemmed | PRR11 promotes ccRCC tumorigenesis by regulating E2F1 stability |
| title_short | PRR11 promotes ccRCC tumorigenesis by regulating E2F1 stability |
| title_sort | prr11 promotes ccrcc tumorigenesis by regulating e2f1 stability |
| topic | Cell biology Nephrology |
| url | https://doi.org/10.1172/jci.insight.145172 |
| work_keys_str_mv | AT simingchen prr11promotesccrcctumorigenesisbyregulatinge2f1stability AT zhiwenhe prr11promotesccrcctumorigenesisbyregulatinge2f1stability AT tianchenpeng prr11promotesccrcctumorigenesisbyregulatinge2f1stability AT fenfangzhou prr11promotesccrcctumorigenesisbyregulatinge2f1stability AT gangwang prr11promotesccrcctumorigenesisbyregulatinge2f1stability AT kaiyuqian prr11promotesccrcctumorigenesisbyregulatinge2f1stability AT lingaoju prr11promotesccrcctumorigenesisbyregulatinge2f1stability AT yuxiao prr11promotesccrcctumorigenesisbyregulatinge2f1stability AT xinghuanwang prr11promotesccrcctumorigenesisbyregulatinge2f1stability |