PDF(Pubmed)
Abstract：
A macroscopic perspective is indispensable for understanding the intricate relationship between deubiquitinases and tumorigenesis. Proteomics has been proposed as a viable approach for elucidating the complex role of deubiquitylation in cellular progression. Instead of studying the function of a single ubiquitinase, research on a deubiquitinase family with similar catalytic core(s) may provide a new perspective for the pathological understanding of cancer. The Ubiquitin C-terminal hydrolase L (UCHL) family consists of four members: UCHL1, UCHL3, UCHL5, and BRAC1 associated protein-1 (BAP1), and they have been implicated in tumorigenesis and metastasis. Some members are considered hallmarks of intracranial lesions, colon cancer, chromatin remodeling, and histone stability. The present study uncovered an unknown correlation between the UCHL family and renal cancer. We discovered that UCHLs exhibit diverse regulatory effects in renal cancer, establishing connections between the renal cancer and truncated gene mutations, mitochondrial energetic metastasis, immune cell infiltration, and chromosomal stability of UCHLs family. Notably, we found that the increase of UCHL5 expression in renal cancer cells decreases the antigen processing and presentation of RCC tumor-infiltrating B cells. Further research identified that the expression of UCHL5 in RCC tumors is correlated with transport proteins, which led us to find that the abundance of UCHL5 in the blood of late-stage renal cell cancer patients is upregulated from 18 ng/L to 500 ng/L. Therefore, we propose that the abundance of UCHL5 in patients\' blood can be a possible indicator of poor prognosis for renal cell cancer.
摘要：
宏观视角对于理解去泛素酶与肿瘤发生之间的复杂关系是必不可少的。蛋白质组学已被提出作为阐明去泛素化在细胞进展中的复杂作用的可行方法。而不是研究单个泛素酶的功能，对具有相似催化核心的去泛素酶家族的研究可能为癌症的病理学理解提供新的视角。泛素C末端水解酶L（UCHL）家族由四个成员组成：UCHL1，UCHL3，UCHL5和BRAC1相关蛋白1（BAP1），它们与肿瘤发生和转移有关。一些成员被认为是颅内病变的标志，结肠癌,染色质重塑，和组蛋白稳定性。本研究揭示了UCHL家族与肾癌之间的未知相关性。我们发现UCHL在肾癌中表现出不同的调节作用，在肾癌和截断的基因突变之间建立联系，线粒体能量转移，免疫细胞浸润，和UCHLs家族的染色体稳定性。值得注意的是,我们发现肾癌细胞中UCHL5表达的增加降低了RCC肿瘤浸润B细胞的抗原加工和呈递。进一步的研究发现，UCHL5在RCC肿瘤中的表达与转运蛋白有关，这导致我们发现晚期肾细胞癌患者血液中UCHL5的丰度从18ng/L上调至500ng/L。因此,我们认为，患者血液中UCHL5的丰度可能是肾细胞癌预后不良的一个指标。
