RNF7 inhibits apoptosis and sunitinib sensitivity and promotes glycolysis in renal cell carcinoma via the SOCS1/JAK/STAT3 feedback loop
Abstract Background RING finger protein 7 (RNF7) is a highly conserved protein that functions as an E3 ubiquitin ligase. RNF7 overexpression is indicated in multiple human cancers, but its role in renal cell carcinoma (RCC) and the mechanisms underlying how it regulates the initiation and progressio...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | Cellular & Molecular Biology Letters |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s11658-022-00337-5 |
| _version_ | 1818203758779170816 |
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| author | Chengwu Xiao Wei Zhang Meimian Hua Huan Chen Bin Yang Ye Wang Qing Yang |
| author_facet | Chengwu Xiao Wei Zhang Meimian Hua Huan Chen Bin Yang Ye Wang Qing Yang |
| author_sort | Chengwu Xiao |
| collection | DOAJ |
| description | Abstract Background RING finger protein 7 (RNF7) is a highly conserved protein that functions as an E3 ubiquitin ligase. RNF7 overexpression is indicated in multiple human cancers, but its role in renal cell carcinoma (RCC) and the mechanisms underlying how it regulates the initiation and progression of RCC have not been explored. Methods Bioinformatics analysis, quantitative reverse-transcription polymerase chain reaction (RT-PCR), and Western blot were conducted to determine the expression of RNF7 in RCC tissues and cell lines. Knockdown and overexpression experiments were performed to examine the effects of RNF7 on cell viability, apoptosis, and glycolysis in vitro and on tumor growth in nude mice in vivo. Results The elevated RNF7 expression in tumor tissues of patients with RCC was correlated with poor survival. RNF7 overexpression inhibited apoptosis and promoted glycolysis in vitro and increased tumor growth in vivo by activating the JAK/STAT3 signaling pathway by ubiquitination of SOCS1. Moreover, RNF7 overexpression affected the sensitivity of RCC cells to sunitinib. Finally, STAT3 activation was necessary for transcriptional induction of RNF7. Conclusion These results demonstrate that RNF7 inhibited apoptosis, promoted glycolysis, and inhibited sunitinib sensitivity in RCC cells via ubiquitination of SOCS1, thus activating STAT3 signaling. These suggest the potential for targeting the RNF7-SOCS1/JAK/STAT3 pathway for RCC treatment. |
| first_indexed | 2024-12-12T03:30:26Z |
| format | Article |
| id | doaj.art-da11b3947cff4a49ad3e71dda1f7e61b |
| institution | Directory Open Access Journal |
| issn | 1425-8153 1689-1392 |
| language | English |
| last_indexed | 2024-12-12T03:30:26Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Cellular & Molecular Biology Letters |
| spelling | doaj.art-da11b3947cff4a49ad3e71dda1f7e61b2022-12-22T00:39:55ZengBMCCellular & Molecular Biology Letters1425-81531689-13922022-05-0127112210.1186/s11658-022-00337-5RNF7 inhibits apoptosis and sunitinib sensitivity and promotes glycolysis in renal cell carcinoma via the SOCS1/JAK/STAT3 feedback loopChengwu Xiao0Wei Zhang1Meimian Hua2Huan Chen3Bin Yang4Ye Wang5Qing Yang6Department of Urology, Changhai Hospital, Naval Medical UniversityDepartment of Urology, Changhai Hospital, Naval Medical UniversityDepartment of Urology, Changhai Hospital, Naval Medical UniversityDepartment of Urology, Changhai Hospital, Naval Medical UniversityDepartment of Urology, Changhai Hospital, Naval Medical UniversityDepartment of Urology, Changhai Hospital, Naval Medical UniversityDepartment of Urology, Changhai Hospital, Naval Medical UniversityAbstract Background RING finger protein 7 (RNF7) is a highly conserved protein that functions as an E3 ubiquitin ligase. RNF7 overexpression is indicated in multiple human cancers, but its role in renal cell carcinoma (RCC) and the mechanisms underlying how it regulates the initiation and progression of RCC have not been explored. Methods Bioinformatics analysis, quantitative reverse-transcription polymerase chain reaction (RT-PCR), and Western blot were conducted to determine the expression of RNF7 in RCC tissues and cell lines. Knockdown and overexpression experiments were performed to examine the effects of RNF7 on cell viability, apoptosis, and glycolysis in vitro and on tumor growth in nude mice in vivo. Results The elevated RNF7 expression in tumor tissues of patients with RCC was correlated with poor survival. RNF7 overexpression inhibited apoptosis and promoted glycolysis in vitro and increased tumor growth in vivo by activating the JAK/STAT3 signaling pathway by ubiquitination of SOCS1. Moreover, RNF7 overexpression affected the sensitivity of RCC cells to sunitinib. Finally, STAT3 activation was necessary for transcriptional induction of RNF7. Conclusion These results demonstrate that RNF7 inhibited apoptosis, promoted glycolysis, and inhibited sunitinib sensitivity in RCC cells via ubiquitination of SOCS1, thus activating STAT3 signaling. These suggest the potential for targeting the RNF7-SOCS1/JAK/STAT3 pathway for RCC treatment.https://doi.org/10.1186/s11658-022-00337-5ApoptosisClear cell renal cell carcinomaGlycolysisJAK/STAT3RNF7SOCS1 |
| spellingShingle | Chengwu Xiao Wei Zhang Meimian Hua Huan Chen Bin Yang Ye Wang Qing Yang RNF7 inhibits apoptosis and sunitinib sensitivity and promotes glycolysis in renal cell carcinoma via the SOCS1/JAK/STAT3 feedback loop Cellular & Molecular Biology Letters Apoptosis Clear cell renal cell carcinoma Glycolysis JAK/STAT3 RNF7 SOCS1 |
| title | RNF7 inhibits apoptosis and sunitinib sensitivity and promotes glycolysis in renal cell carcinoma via the SOCS1/JAK/STAT3 feedback loop |
| title_full | RNF7 inhibits apoptosis and sunitinib sensitivity and promotes glycolysis in renal cell carcinoma via the SOCS1/JAK/STAT3 feedback loop |
| title_fullStr | RNF7 inhibits apoptosis and sunitinib sensitivity and promotes glycolysis in renal cell carcinoma via the SOCS1/JAK/STAT3 feedback loop |
| title_full_unstemmed | RNF7 inhibits apoptosis and sunitinib sensitivity and promotes glycolysis in renal cell carcinoma via the SOCS1/JAK/STAT3 feedback loop |
| title_short | RNF7 inhibits apoptosis and sunitinib sensitivity and promotes glycolysis in renal cell carcinoma via the SOCS1/JAK/STAT3 feedback loop |
| title_sort | rnf7 inhibits apoptosis and sunitinib sensitivity and promotes glycolysis in renal cell carcinoma via the socs1 jak stat3 feedback loop |
| topic | Apoptosis Clear cell renal cell carcinoma Glycolysis JAK/STAT3 RNF7 SOCS1 |
| url | https://doi.org/10.1186/s11658-022-00337-5 |
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