Succinylation Regulators Promote Clear Cell Renal Cell Carcinoma by Immune Regulation and RNA N6-Methyladenosine Methylation
Author
Lu, WenqingChe, Xiaofang
Qu, Xiujuan
Zheng, Chunlei
Yang, Xianghong
Bao, Bowen
Li, Zhi
Wang, Duo
Jin, Yue
Wang, Yizhe
Xiao, Jiawen
Qi, Jianfei
Liu, Yunpeng
Date
2021-02-18Journal
Frontiers in Cell and Developmental BiologyPublisher
Frontiers Media S.A.Type
Article
Metadata
Show full item recordAbstract
Succinylation is a newly discovered and multienzyme-regulated post-translational modification (PTM) that is associated with the initiation and progression of cancer. Currently, no systematic analyses on the role of succinylation regulators in tumors have been reported. In this study, we performed a comprehensive pan-cancer analysis on four well-known succinylation regulators (CPT1A, KAT2A, SIRT5, and SIRT7). We found that these regulators played specific and critical roles in the prognosis of clear cell renal cell carcinoma (ccRCC). We constructed a risk score (RS) based on two independent prognostic prediction factors, CPT1A and KAT2A, and subsequently developed a nomogram model containing the RS, which showed good accuracy in the prediction of overall survival (OS) in ccRCC patients. Furthermore, we used the similar expression pattern of four succinylation regulators according to consensus clustering analysis to divide the patients into three clusters that exhibited prominently different OS as well as clinicopathological characteristics. Differently expressed genes (DEGs) and pathway enrichment analyses of three clusters indicated that succinylation regulators might promote malignant progression of ccRCC by regulating the infiltration of immune cells and RNA N6-methyladenosine (m6A) methylation. Importantly, our data suggest that CPT1A and SIRT5 might up-regulate and down-regulate the expression of LRPPRC and EIF3B, respectively. Our study systematically analyzed the prognostic predictive values of four succinylation regulators and revealed their potential mechanisms in ccRCC aggressiveness. These data provide new insight into the understanding of succinylation modification and present clinical evidence for its role in ccRCC treatments.Rights/Terms
Copyright © 2021 Lu, Che, Qu, Zheng, Yang, Bao, Li, Wang, Jin, Wang, Xiao, Qi and Liu.Keyword
RNA N6-methyladenosine methylationclear cell renal cell carcinoma
immune
prognosis
succinylation regulators
Identifier to cite or link to this item
http://hdl.handle.net/10713/14976ae974a485f413a2113503eed53cd6c53
10.3389/fcell.2021.622198