SETD7 Promotes Cell Proliferation and Migration via Methylation-mediated TAF7 in Clear Cell Renal Cell Carcinoma

Zhang, Jinyuan; Duan, Baojun; Li, Fang; Jing, Xintao; Li, Rufeng; Cai, Shuang; Cao, Li; Jiang, Qiuyu; Zhou, Jing; Zhou, Jiancheng; Qin, Yannan; Wang, Xiaofei; Tong, Dongdong; Huang, Chen

doi:10.7150/ijbs.93201

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Int J Biol Sci 2024; 20(8):3008-3027. doi:10.7150/ijbs.93201 This issue Cite

Research Paper

SETD7 Promotes Cell Proliferation and Migration via Methylation-mediated TAF7 in Clear Cell Renal Cell Carcinoma

Jinyuan Zhang^1#, Baojun Duan^1,2#, Fang Li¹, Xintao Jing¹, Rufeng Li¹, Shuang Cai¹, Li Cao¹, Qiuyu Jiang¹, Jing Zhou¹, Jiancheng Zhou³, Yannan Qin¹, Xiaofei Wang¹, Dongdong Tong^1✉, Chen Huang^1✉

1. Institute of Genetics and Development Biology, Translational Medcine Institute, Xi'an Jiaotong University, Xi'an 710301, China.
2. Department of Medical Oncology of Shaanxi Provincial People's Hospital, Xi'an 710068, China.
3. Department of Urology of Shaanxi Provincial People's Hospital, Xi'an 710068, China.
#These authors contributed equally: Jinyuan Zhang, Baojun Duan.

Citation:

Zhang J, Duan B, Li F, Jing X, Li R, Cai S, Cao L, Jiang Q, Zhou J, Zhou J, Qin Y, Wang X, Tong D, Huang C. SETD7 Promotes Cell Proliferation and Migration via Methylation-mediated TAF7 in Clear Cell Renal Cell Carcinoma. Int J Biol Sci 2024; 20(8):3008-3027. doi:10.7150/ijbs.93201. https://www.ijbs.com/v20p3008.htm

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Abstract

SET domain containing 7(SETD7), a member of histone methyltransferases, is abnormally expressed in multiple tumor types. However, the biological function and underlying molecular mechanism of SETD7 in clear cell renal cell carcinoma (ccRCC) remain unclear. Here, we explored the biological effects of SETD7-TAF7-CCNA2 axis on proliferation and metastasis in ccRCC. We identified both SETD7 and TAF7 were up-regulated and significantly promoted the proliferation and migration of ccRCC cells. Concurrently, there was a significant positive correlation between the expression of SETD7 and TAF7, and the two were colocalized in the nucleus. Mechanistically, SETD7 methylates TAF7 at K5 and K300 sites, resulting in the deubiquitination and stabilization of TAF7. Furthermore, re-expression of TAF7 could partially restore SETD7 knockdown inhibited ccRCC cells proliferation and migration. In addition, TAF7 transcriptionally activated to drive the expression of cyclin A2 (CCNA2). And more importantly, the methylation of TAF7 at K5 and K300 sites exhibited higher transcriptional activity of CCNA2, which promotes formation and progression of ccRCC. Our findings reveal a unique mechanism that SETD7 mediated TAF7 methylation in regulating transcriptional activation of CCNA2 in ccRCC progression and provide a basis for developing effective therapeutic strategies by targeting members of SETD7-TAF7-CCNA2 axis.

Keywords: SETD7, oncogene, lysine methylation, TAF7, clear cell renal cell carcinoma

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APA

Zhang, J., Duan, B., Li, F., Jing, X., Li, R., Cai, S., Cao, L., Jiang, Q., Zhou, J., Zhou, J., Qin, Y., Wang, X., Tong, D., Huang, C. (2024). SETD7 Promotes Cell Proliferation and Migration via Methylation-mediated TAF7 in Clear Cell Renal Cell Carcinoma. International Journal of Biological Sciences, 20(8), 3008-3027. https://doi.org/10.7150/ijbs.93201.

ACS

Zhang, J.; Duan, B.; Li, F.; Jing, X.; Li, R.; Cai, S.; Cao, L.; Jiang, Q.; Zhou, J.; Zhou, J.; Qin, Y.; Wang, X.; Tong, D.; Huang, C. SETD7 Promotes Cell Proliferation and Migration via Methylation-mediated TAF7 in Clear Cell Renal Cell Carcinoma. Int. J. Biol. Sci. 2024, 20 (8), 3008-3027. DOI: 10.7150/ijbs.93201.

NLM

CSE

Zhang J, Duan B, Li F, Jing X, Li R, Cai S, Cao L, Jiang Q, Zhou J, Zhou J, Qin Y, Wang X, Tong D, Huang C. 2024. SETD7 Promotes Cell Proliferation and Migration via Methylation-mediated TAF7 in Clear Cell Renal Cell Carcinoma. Int J Biol Sci. 20(8):3008-3027.

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