Hu Xiao, Zhu Zhu, Liu Kehan, Liu Jinlin, Li Jingpei, Wang Zhengyang
Academy of Medical Science, Zhengzhou University, Zhengzhou, China.
Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Transl Cancer Res. 2024 Jan 31;13(1):102-111. doi: 10.21037/tcr-23-124. Epub 2024 Jan 29.
Hepatocellular carcinoma (HCC) is an aggressive malignancy that poses a serious threat to human life. The conventional therapies for HCC cannot substantially improve overall survival (OS), disease duration, and prognosis. Therefore, it is important to study the underlying mechanism of HCC and seek better methods for HCC prevention and treatment. Ubiquitination is a post-translational modification that modulates great cellular function by cooperating with E1, E2, and E3 ligases. Yet, the ubiquitination and lysine residues in HCC are still elusive. Seven in absentia homolog 1 (), as an important E3 ubiquitin ligase, regulates ubiquitin-mediated proteolysis to function as a tumor suppressor in HCC. In the present study, we downregulated in the mouse HCC cell line Hepa1-6 and studied its function by using proteome-wide identification.
was knocked down by short hairpin RNA (shRNA) in mouse HCC cell line Hepa1-6 cells, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was conducted to analyze the ubiquitinated proteins. Functional analysis was performed using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment.
The systematic profiling showed a total of 550 differently expressed proteins (DEPs), including 263 upregulated DEPs and 287 downregulated DEPs. Considering the amino acid sequences around the modified lysine residues, seven proteins were identified as conserved ubiquitination motifs in the peptides. The ubiquitinated proteins were mainly distributed in the cytoplasm, nucleus, and plasma membrane. Functional analysis suggested that the ubiquitinated proteins were mostly enriched in the nucleus, cytoplasm, and extracellular space; in addition, the ubiquitinated proteins were mostly attributed to the protein binding, and disease. The ubiquitinated proteins modulate HCC by mapping lysine modification sites.
The use of high-throughput characterization to identify novel and specific targets associated with is of great significance in terms of functional weight. The results obtained in this paper from the analysis of proteomic data provided novel insights into ubiquitination regulation in HCC, which pave the way for further research and mechanism discovery of HCC.
肝细胞癌（HCC）是一种侵袭性恶性肿瘤，对人类生命构成严重威胁。HCC的传统治疗方法无法显著提高总生存期（OS）、疾病持续时间和预后。因此，研究HCC的潜在机制并寻找更好的HCC预防和治疗方法具有重要意义。泛素化是一种翻译后修饰，通过与E1、E2和E3连接酶协同作用来调节多种细胞功能。然而，HCC中的泛素化和赖氨酸残基仍不清楚。无七同源物1（）作为一种重要的E3泛素连接酶，调节泛素介导的蛋白水解，在HCC中发挥肿瘤抑制作用。在本研究中，我们在小鼠HCC细胞系Hepa1-6中下调，并通过全蛋白质组鉴定研究其功能。
在小鼠HCC细胞系Hepa1-6细胞中用短发夹RNA（shRNA）敲低，进行液相色谱-串联质谱（LC-MS/MS）分析以分析泛素化蛋白。使用京都基因与基因组百科全书（KEGG）和基因本体论（GO）富集进行功能分析。
系统分析显示共有550种差异表达蛋白（DEP），包括263种上调的DEP和287种下调的DEP。考虑到修饰赖氨酸残基周围的氨基酸序列，七种蛋白被鉴定为肽中的保守泛素化基序。泛素化蛋白主要分布在细胞质、细胞核和质膜中。功能分析表明，泛素化蛋白大多富集在细胞核、细胞质和细胞外空间；此外，泛素化蛋白大多归因于蛋白质结合和疾病。泛素化蛋白通过定位赖氨酸修饰位点来调节HCC。
利用高通量表征鉴定与相关的新的特异性靶点在功能权重方面具有重要意义。本文从蛋白质组学数据分析中获得的结果为HCC中泛素化调控提供了新的见解，为HCC的进一步研究和机制发现铺平了道路。
