Open Access

ARTICLE

RNF26 up-regulates PD-L1 to regulate the cancer immune response in ccRCC

by WEIGANG REN^1,#, JING LI^2,#, RUIJIANG ZENG^3,4, LIANG ZHU^3,4,*

1 Department of Urology, Hunan Provincial People’s Hospital, Hunan Normal University, Changsha, 410000, China
2 Department of Rehabilitation, The Second Xiangya Hospital, Central South University, Changsha, 410000, China
3 Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, 410000, China
4 Uro-Oncology Institute of Central South University, Changsha, 410000, China

* Corresponding Author: LIANG ZHU. Email:
# These authors contributed equally

BIOCELL 2024, 48(9), 1323-1330. https://doi.org/10.32604/biocell.2024.051747

Received 14 March 2024; Accepted 12 July 2024; Issue published 04 September 2024

Abstract

Background: Clear cell renal cell carcinoma (ccRCC) stands as the most prevalent form of kidney cancer, accounting for a significant proportion of malignancies affecting the kidneys. ccRCC is well known as a type of tumour with immunogenicity. Immune checkpoint inhibitors (ICIs) aim to enhance the anticancer immune response in ccRCC by blocking programmed cell death 1 ligand 1/programmed death 1 (PD-L1/PD-1) pathways. In a previous study, we showed that RING finger protein 26 (RNF26) degrades chromobox 7 (CBX7) to activate the tumor necrosis factor (TNF) in ccRCC. Methods: We analyzed The Cancer Genome Atlas (TCGA) database using the R package ESTIMATE and found that RNF26 was significantly associated with ccRCC immune infiltration. The relationship between RNF26 and the PD1 checkpoint signaling pathway was detected by enrichment analysis. In addition, the molecular mechanism of RNF26 up-regulation of PD-L1 was detected by transcriptome sequencing, RT-qPCR, and Western Blot in ccRCC cell lineages 786-O and A498 cells. The transplantation tumor experiments in C57BL/6 mice were used to test the efficacy of anti-PD1 and knockdown of RNF26 in vivo. Results: We showed that RNF26 suppressed the immune response to ccRCC. Next, we revealed that RNF26 activated the PD-1 checkpoint pathway to suppress the immune response to ccRCC, possibly via the CBX7/PD-L1 axis. Conclusion: The suggestion derived from our results is that targeting RNF26 holds the potential to amplify the efficacy of anticancer immunotherapies in the treatment of ccRCC.

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Supplementary Material

Supplementary Material File

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