Upregulation of ERp57 promotes clear cell renal cell carcinoma progression by initiating a STAT3/ILF3 feedback loop
Abstract Background ERp57 dysfunction has been shown to contribute to tumorigenesis in multiple malignances. However, the role of ERp57 in clear cell renal carcinoma (ccRCC) remains unclear. Methods Cell proliferation ability was measured by MTT and colony forming assays. Western blotting and quanti...
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| Format: | Article |
| Language: | English |
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BMC
2019-10-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
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| Online Access: | http://link.springer.com/article/10.1186/s13046-019-1453-z |
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| author | Yan Liu Jian-Xing Wang Zi-Yuan Nie Yue Wen Xin-Ju Jia Li-Na Zhang Hui-Jun Duan Yong-Hong Shi |
| author_facet | Yan Liu Jian-Xing Wang Zi-Yuan Nie Yue Wen Xin-Ju Jia Li-Na Zhang Hui-Jun Duan Yong-Hong Shi |
| author_sort | Yan Liu |
| collection | DOAJ |
| description | Abstract Background ERp57 dysfunction has been shown to contribute to tumorigenesis in multiple malignances. However, the role of ERp57 in clear cell renal carcinoma (ccRCC) remains unclear. Methods Cell proliferation ability was measured by MTT and colony forming assays. Western blotting and quantitative real-time PCR (qRT-PCR) were performed to measure protein and mRNA expression. Co-immunoprecipitation (CoIP) and proximity ligation assay (PLA) were performed to detect protein-protein interaction. Chromatin immunoprecipitation (ChIP), ribonucleoprotein immunoprecipitation (RIP), and oligo pull-down were used to confirm DNA–protein and RNA–protein interactions. Promoter luciferase analysis was used to detect transcription factor activity. Results Here we found ERp57 was overexpressed in ccRCC tissues, and the higher levels of ERp57 were correlated with poor survival in patients with ccRCC. In vivo and in vitro experiments showed that ccRCC cell proliferation was enhanced by ERp57 overexpression and inhibited by ERp57 deletion. Importantly, we found ERp57 positively regulated ILF3 expression in ccRCC cells. Mechanically, ERp57 was shown to bind to STAT3 protein and enhance the STAT3-mediated transcriptional activity of ILF3. Furthermore, ILF3 levels were increased in ccRCC tissues and associated with poor prognosis. Interestingly, we revealed that ILF3 could bind to ERp57 and positively regulate its expression by enhancing its mRNA stability. Furthermore, ccRCC cell proliferation was moderated via the ERp57/STAT3/ILF3 feedback loop. Conclusions In summary, our results indicate that the ERp57/STAT3/ILF3 feedback loop plays a key role in the oncogenesis of ccRCC and provides a potential therapeutic target for ccRCC treatment. |
| first_indexed | 2024-12-12T08:59:58Z |
| format | Article |
| id | doaj.art-68d069f27eaa4c20b9855f957f310324 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-12T08:59:58Z |
| publishDate | 2019-10-01 |
| publisher | BMC |
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| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-68d069f27eaa4c20b9855f957f3103242022-12-22T00:29:52ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662019-10-0138111710.1186/s13046-019-1453-zUpregulation of ERp57 promotes clear cell renal cell carcinoma progression by initiating a STAT3/ILF3 feedback loopYan Liu0Jian-Xing Wang1Zi-Yuan Nie2Yue Wen3Xin-Ju Jia4Li-Na Zhang5Hui-Jun Duan6Yong-Hong Shi7Department of Pathology, Hebei Medical UniversityDepartment of Pathology, Hebei Medical UniversityDepartment of Hematology, The Second Hospital of Hebei Medical UniversityDepartment of Pathology, Hebei Medical UniversityDepartment of Endocrinology, The First Hospital of Hebei Medical UniversityDepartment of Pathology, Hebei Medical UniversityDepartment of Pathology, Hebei Medical UniversityDepartment of Pathology, Hebei Medical UniversityAbstract Background ERp57 dysfunction has been shown to contribute to tumorigenesis in multiple malignances. However, the role of ERp57 in clear cell renal carcinoma (ccRCC) remains unclear. Methods Cell proliferation ability was measured by MTT and colony forming assays. Western blotting and quantitative real-time PCR (qRT-PCR) were performed to measure protein and mRNA expression. Co-immunoprecipitation (CoIP) and proximity ligation assay (PLA) were performed to detect protein-protein interaction. Chromatin immunoprecipitation (ChIP), ribonucleoprotein immunoprecipitation (RIP), and oligo pull-down were used to confirm DNA–protein and RNA–protein interactions. Promoter luciferase analysis was used to detect transcription factor activity. Results Here we found ERp57 was overexpressed in ccRCC tissues, and the higher levels of ERp57 were correlated with poor survival in patients with ccRCC. In vivo and in vitro experiments showed that ccRCC cell proliferation was enhanced by ERp57 overexpression and inhibited by ERp57 deletion. Importantly, we found ERp57 positively regulated ILF3 expression in ccRCC cells. Mechanically, ERp57 was shown to bind to STAT3 protein and enhance the STAT3-mediated transcriptional activity of ILF3. Furthermore, ILF3 levels were increased in ccRCC tissues and associated with poor prognosis. Interestingly, we revealed that ILF3 could bind to ERp57 and positively regulate its expression by enhancing its mRNA stability. Furthermore, ccRCC cell proliferation was moderated via the ERp57/STAT3/ILF3 feedback loop. Conclusions In summary, our results indicate that the ERp57/STAT3/ILF3 feedback loop plays a key role in the oncogenesis of ccRCC and provides a potential therapeutic target for ccRCC treatment.http://link.springer.com/article/10.1186/s13046-019-1453-zClear cell renal carcinomaERp57ILF3STAT3Proliferation |
| spellingShingle | Yan Liu Jian-Xing Wang Zi-Yuan Nie Yue Wen Xin-Ju Jia Li-Na Zhang Hui-Jun Duan Yong-Hong Shi Upregulation of ERp57 promotes clear cell renal cell carcinoma progression by initiating a STAT3/ILF3 feedback loop Journal of Experimental & Clinical Cancer Research Clear cell renal carcinoma ERp57 ILF3 STAT3 Proliferation |
| title | Upregulation of ERp57 promotes clear cell renal cell carcinoma progression by initiating a STAT3/ILF3 feedback loop |
| title_full | Upregulation of ERp57 promotes clear cell renal cell carcinoma progression by initiating a STAT3/ILF3 feedback loop |
| title_fullStr | Upregulation of ERp57 promotes clear cell renal cell carcinoma progression by initiating a STAT3/ILF3 feedback loop |
| title_full_unstemmed | Upregulation of ERp57 promotes clear cell renal cell carcinoma progression by initiating a STAT3/ILF3 feedback loop |
| title_short | Upregulation of ERp57 promotes clear cell renal cell carcinoma progression by initiating a STAT3/ILF3 feedback loop |
| title_sort | upregulation of erp57 promotes clear cell renal cell carcinoma progression by initiating a stat3 ilf3 feedback loop |
| topic | Clear cell renal carcinoma ERp57 ILF3 STAT3 Proliferation |
| url | http://link.springer.com/article/10.1186/s13046-019-1453-z |
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