The First Affiliated Hospital, Jinan University, 613 W. Huangpu Avenue, Guangzhou, Guangdong, 510632, China.
Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong, 518020, China.
J Transl Med. 2022 Oct 2;20(1):445. doi: 10.1186/s12967-022-03645-8.
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.
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.
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.
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.
根据 2020 年全球癌症统计数据，结直肠癌（CRC）的发病率和死亡率在所有肿瘤中排名第三和第二。泛素化的紊乱在 CRC 的发生和发展中起着重要作用，但 CRC 细胞的泛素组和与生存相关的泛素化仍知之甚少。
我们使用自己的蛋白质组学和泛素蛋白质组学检测数据集来描述 CRC 患者的泛素组（n=6）。然后，根据来自公共数据库的数据组分析，搜索可能与生存相关的泛素化。
对于泛素组学检测，我们鉴定了 1690 个可定量位点和 870 个可定量蛋白。我们发现高度泛素化的蛋白（n≥10）特异性参与 G 蛋白偶联、糖蛋白偶联和抗原呈递等生物学过程。此外，我们还描绘了五种经常被泛素识别的基序序列。随后，我们表明，CRC 细胞与正常相邻细胞相比，1172 种蛋白的泛素化含量上调，1700 种蛋白下调。我们证明，差异泛素化蛋白与代谢、免疫调节和端粒维持等途径有关。然后，我们整合了临床蛋白质组肿瘤分析联盟（CPTAC）（n=98）的蛋白质组数据集，揭示了 FOCAD 在 Lys583 和 Lys587 处的泛素化增加可能与患者生存有关。最后，我们描绘了 FOCAD 的突变图谱，并阐明了其在 CRC 中对 RNA 定位和翻译的潜在功能。
本研究描述了 CRC 细胞的泛素组，并鉴定了可能影响患者生存的异常泛素化，从而为临床治疗提供了新的可能机会。
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