The involvement of high succinylation modification in the development of prostate cancer

Abstract

ObjectiveSuccinylation modification of the lysine site plays an important role in tumorigenesis and development, but it is rarely reported in prostate cancer (PCa), so this study aims to elucidate its expression in and clinical correlation with PCa.MethodsA total of 95 tumor, 3 normal and 52 paired adjacent tissue of PCa were involved for succinylation stanning. 498 PCa samples with 20 succinylation modification-related genes from TCGA were downloaded for model construction. Statistical methods were employed to analyze the data, including Non-Negative Matrix Factorization (NMF) algorithm, t-Distributed Stochastic Neighbor Embedding (t-SNE) algorithm and Cox regression analysis.ResultsThe pan-succinyllysine antibody stanning indicated that tumor tissues showed higher succinyllysine level than adjacent tissues (p<0.001). Gleason grade and PDL1 expression levels were significantly different (p<0.001) among the high, medium and low succinylation staining scores. The types of PCa tissue were divided into four clusters using RNA-seq data of 20 succinylation-related genes in TCGA database. Clinical characterize of age, PSA level, and pathological stage showed differences among four clusters. The expression of succinylation-related genes (KAT5, SDHD and GLYATL1) and PCa related genes (PDL1, AR and TP53) were significantly different in 52 matched tumor and adjacent tissues (p<0.001). GLYATL1 and AR gene expression was significantly related to the pathological stage of PCa.ConclusionSuccinylation was significantly increased in PCa tissues and was closely related to Gleason grade and PD-L1 expression. Model construction of 20 genes related to succinylation modification showed that the later the pathological stage of PCa, the higher the level of succinylation modification.

WITHDRAWN: AMPK α Succinylation modification of protein K266 enhances lipid metabolism and promotes growth of non-small cell lung cancer cells

“…Because succinylation modi cation increases the negative charge of proteins, it can cause conformational changes, which may lead to changes in their biological activity or stability [6]. The succinylation of proteins plays an important role in many biological processes, including oxidation, metabolic regulation, and signal transduction, is closely related to the occurrence and development of various human diseases [7]. In various cancers, such as thyroid cancer, breast cancer, lung cancer, and colon cancer, the succinylation of proteins promotes tumour proliferation, differentiation, and metastasis [8].…”

A glimpse into novel acylations and their emerging role in regulating cancer metastasis

“…Decreasing histone Kcr using BRD4 inhibitors can alleviate the proliferation, invasion, and migration of PCa cells [ 171 ]. Analogously, high Ksuc levels were also detected in cancer tissues of patients with PCa compared with adjacent and normal prostate tissues [ 172 ]. Nevertheless, for patients with PCa and Gleason grades III–IV, the Ksuc modification was highly overexpressed, demonstrating its close relationship with the degree of invasion, metastasis, malignancy, and prognosis of PCa [ 173 ].…”

Emerging therapeutic frontiers in cancer: insights into posttranslational modifications of PD-1/PD-L1 and regulatory pathways

“…Succinylation correlates with increased PD-L1 expression in prostate cancer, suggesting its significant role in regulating PD-L1 levels [ 118 – 121 ]. Additionally, lactic acid, a precursor of histone lysine modifications, is linked to glycolytic gene activation by STAT5 in AML, leading to increased PD-L1 transcription via enhanced histone lactylation and nuclear translocation of E3BP [ 122 , 123 ].…”