Comprehensive characterization of ubiquitinome of human colorectal cancer and identification of potential survival-related ubiquitination

Abstract

Background According to the Global Cancer Statistics in 2020, the incidence and mortality of colorectal cancer (CRC) rank third and second among all tumors. The disturbance of ubiquitination plays an important role in the initiation and development of CRC, but the ubiquitinome of CRC cells and the survival-relevant ubiquitination are poorly understood. Methods The ubiquitinome of CRC patients (n = 6) was characterized using our own data sets of proteomic and ubiquitin-proteomic examinations. Then, the probable survival-relevant ubiquitination was searched based on the analyses of data sets from public databases. Results For the ubiquitinomic examination, we identified 1690 quantifiable sites and 870 quantifiable proteins. We found that the highly-ubiquitinated proteins (n ≥ 10) were specifically involved in the biological processes such as G-protein coupling, glycoprotein coupling, and antigen presentation. Also, we depicted five motif sequences frequently recognized by ubiquitin. Subsequently, we revealed that the ubiquitination content of 1172 proteins were up-regulated and 1700 proteins were down-regulated in CRC cells versus normal adjacent cells. We demonstrated that the differentially ubiquitinated proteins were relevant to the pathways including metabolism, immune regulation, and telomere maintenance. Then, integrated with the proteomic datasets from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) (n = 98), we revealed that the increased ubiquitination of FOCAD at Lys583 and Lys587 was potentially associated with patient survival. Finally, we depicted the mutation map of FOCAD and elucidated its potential functions on RNA localization and translation in CRC. Conclusions The findings of this study described the ubiquitinome of CRC cells and identified abnormal ubiquitination(s) potentially affecting the patient survival, thereby offering new probable opportunities for clinical treatment.

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

“…In addition, preliminary progress has also been made in the acetylome, ubiquitinome and glycosylome in clinical samples. 140 , 141 , 148 , 161 , 1486 , 1487 , 1488 , 1489 However, studies of the relationship between many other types of protein modifications and diseases in large clinical cohorts remain lacking. The establishment of a multiomics molecular network based on the genome, proteome, PTMome, and metabolome will provide new breakthroughs for the discovery of new biomarkers and drug targets.…”

“…Some phosphosites are closely related to the occurrence and development of these diseases. In addition, preliminary progress has also been made in the acetylome, ubiquitinome and glycosylome in clinical samples 140,141,148,1486–1489,161 . However, studies of the relationship between many other types of protein modifications and diseases in large clinical cohorts remain lacking.…”

Comprehensive transcriptomic analysis identifies SLC25A4 as a key predictor of prognosis in osteosarcoma

“…In recent years, screening for genetic changes has led to the identification of DEGs and functional pathways involved in tumor development, providing a biological basis for early diagnosis and treatment strategies. ( Wang et al, 2022 ; Zhang et al, 2022 ).…”

Global profiling of lysine ubiquitylation in human hypothalamus

“…The field of ubiquitinomics has emerged as a potent tool for elucidating human diseases, exemplified by recent studies in pituitary adenomas [7], adrenocortical hormone-secreting adenomas [8], colorectal cancer [9][10], and lung cancer [11][12]. Noteworthy contributions include the insights from Wu et al (2015) [11] and Zhao et al (2022) [8] on molecular interactions in non-small cell lung cancer and corticotroph adenomas, respectively, alongside revelations by Zhang et al (2022) [9] and Yuan et al (2019) [10] regarding the colorectal cancer ubiquitinome and its oncogenic roles in colon cancer. Additionally, Zhan et al (2022) [12] have elucidated pathway alterations in lung squamous cell carcinomas.…”