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PMID: 37747077 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

RCC1 functions as a tumor facilitator in clear cell renal cell carcinoma by dysregulating cell cycle, apoptosis, and EZH2 stability.

Cancer medicine ·Vol. 12 ·No. 19 ·2023-00-00 ·Pages 19889-19903

Wu Y, Xu Z, Chen X, Fu G, Tian J, Jin B

Abstract

RCC1 functions as a pivotal guanine nucleotide exchange factor and was reported to be involved in mitosis, the assembly of the nuclear envelope, nucleocytoplasmic transport in cell physiological processes. Recent studies reported that RCC1 could regulate immunological pathways and promote the growth of some malignant solid tumors. However, the prognostic value and exact function of RCC1 remain unknown in patients with clear cell renal cell carcinoma (cRCC). The UALCAN and KM plotter portals were used to analyze the expression profile and related tumor prognosis of RCC1 in ccRCC using data from TCGA. The expression profile of RCC1 was also confirmed in clinical samples using qRT-PCR, western blotting, and immunohistochemistry. The role of RCC1 on ccRCC cells in vitro was confirmed by a series of functional assays. Animal experiments were performed to verify the suppressive effect of RCC1 knockdown on tumor growth in vivo. The correlation of RCC1 expression with that of EZH2 was explored in clinical samples using IHC. The interaction between RCC1 and EZH2 was further verified using a CO-IP assay and a protein stability assay. RCC1 was upregulated in ccRCC tissues compared with normal tissues in TCGA dataset and paired clinical samples. RCC1 promoted ccRCC progression by accelerating the cell cycle and suppressing apoptosis. In addition, RCC1 could bind EZH2 and regulate its expression at the posttranscriptional level. RCC1 and EZH2 expression showed a strong correlation in clinical samples. Further investigation proved that RCC1 regulated EZH2 protein stability through the ubiquitin-proteasome pathway. RCC1 could be a potential therapeutic target in ccRCC. The RCC1/EZH2 axis takes part in the development of ccRCC.

Keywords
EZH2 RCC1 apoptosis cell cycle clear cell renal cell carcinoma
MeSH Terms
Animals Humans Carcinoma, Renal Cell/pathology Cell Proliferation Cell Cycle/genetics Prognosis Apoptosis Kidney Neoplasms/pathology Cell Line, Tumor Enhancer of Zeste Homolog 2 Protein/genetics,metabolism Nuclear Proteins Cell Cycle Proteins/genetics,metabolism Guanine Nucleotide Exchange Factors/genetics
Chemicals
EZH2 protein, human Enhancer of Zeste Homolog 2 Protein RCC1 protein, human Nuclear Proteins Cell Cycle Proteins Guanine Nucleotide Exchange Factors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Wu Yunfei
Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. | Zhejiang Engineering Research Center for Urinary Bladder Carcinoma Innovation Diagnosis and Treatment, Hangzhou, China.
Xu Zhijie
Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. | Zhejiang Engineering Research Center for Urinary Bladder Carcinoma Innovation Diagnosis and Treatment, Hangzhou, China.
Chen Xiaoyi
Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. | Zhejiang Engineering Research Center for Urinary Bladder Carcinoma Innovation Diagnosis and Treatment, Hangzhou, China.
Fu Guanghou ORCID
Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. | Zhejiang Engineering Research Center for Urinary Bladder Carcinoma Innovation Diagnosis and Treatment, Hangzhou, China.
Tian Junjie
Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. | Zhejiang Engineering Research Center for Urinary Bladder Carcinoma Innovation Diagnosis and Treatment, Hangzhou, China.
Jin Baiye ORCID
Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. | Zhejiang Engineering Research Center for Urinary Bladder Carcinoma Innovation Diagnosis and Treatment, Hangzhou, China.
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Article Info
Journal
Cancer medicine
Abbr.
Cancer Med
ISSN
2045-7634
DOI
10.1002/cam4.6594
Published
2023-00-00
Epub
2023-00-25
Pages
19889-19903
Language
English
Region
United States
NLM ID
101595310
PMCID
PMC10587970
Subset
IM
External Links
PubMed source DOI: 10.1002/cam4.6594 PMC Full Text View journal details
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