Int J Biol Sci 2022; 18(5):2132-2145. doi:10.7150/ijbs.69325 This issue

Research Paper

The RNF26/CBX7 axis modulates the TNF pathway to promote cell proliferation and regulate sensitivity to TKIs in ccRCC

Wentao Liu1,2,3*, Haohui Wang1,2,3*, Chengzhu Jian1,2*, Wei Li1,2, Kun Ye2, Jiannan Ren1,2, Liang Zhu1,2, Yinhuai Wang1, Xin Jin1,2✉, Lu Yi1,2,3✉

1. Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China
2. Uro-Oncology Institute of Central South University, Changsha, Hunan, 410011, China
3. Hunan Engineering Research Center of Smart and Precise Medicine, Changsha, Hunan, 410011, China
*These authors contributed equally.

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Citation:
Liu W, Wang H, Jian C, Li W, Ye K, Ren J, Zhu L, Wang Y, Jin X, Yi L. The RNF26/CBX7 axis modulates the TNF pathway to promote cell proliferation and regulate sensitivity to TKIs in ccRCC. Int J Biol Sci 2022; 18(5):2132-2145. doi:10.7150/ijbs.69325. Available from https://www.ijbs.com/v18p2132.htm

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Abstract

Graphic abstract

Clear cell renal cell carcinoma (ccRCC) accounts for 85% of all malignant renal tumors. Currently, the pathogenesis of ccRCC is not fully understood. Chromobox (CBX) family proteins are the major subunits of PcG complexes and are implicated in regulating mammalian development. The CBX family consists of eight members, namely, CBX1-8. Numerous studies have highlighted that each CBX protein exhibits distinct functions and prognostic roles in specific cancer types. In this study, in silico analysis indicated that CBX7 was downregulated in ccRCC and correlated with favorable prognosis in a ccRCC cohort. Subsequent studies showed that CBX7 inhibited cancer cell proliferation and invasion. Then, we showed that CBX7 downregulated ETS1 to inactivate the tumor necrosis factor (TNF) signaling pathway, which inhibited tumor proliferation and enhanced the sensitivity of ccRCC cells to tyrosine kinase inhibitors (TKIs). Moreover, we found that CBX7 was a bona fide substrate of RNF26. RNF26 promoted the degradation of CBX7 and enhanced ccRCC tumor growth. Therefore, our results revealed a novel RNF26/CBX7 axis that modulates the TNF signaling pathway in ccRCC.

Keywords: CBX7, RNF26, TNF signaling pathway, clear cell renal cell carcinoma