Tang Yu-Xing, Wu Wei-Zi, Zhou Sheng-Sheng, Zeng Da-Tong, Zheng Guang-Cai, He Rong-Quan, Qin Di-Yuan, Huang Wan-Ying, Chen Ji-Tian, Dang Yi-Wu, Tang Yu-Lu, Chi Bang-Teng, Zhan Yan-Ting, Chen Gang
Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
Department of Pathology, People's Hospital of Ling Shan, Nanning 535400, Guangxi Zhuang Autonomous Region, China.
World J Gastrointest Oncol. 2025 May 15;17(5):103594. doi: 10.4251/wjgo.v17.i5.103594.
, a key regulator of the ubiquitination in tumour development, has not been thoroughly studied in hepatocellular carcinoma (HCC).
To elucidate the expression of in HCC and its potential regulatory mechanism related to ubiquitination.
Bulk RNA (RNA sequencing and microarrays), immunohistochemistry (IHC) tissues, and single-cell RNA sequencing (scRNA-seq) data were integrated to comprehensively investigate expression in HCC. Clustered regularly interspaced short palindromic repeats analysis was performed to assess growth in HCC cell lines following knockout. Enrichment analyses were conducted to explore the functions of . ScRNA-seq data was used to examine the cell cycle and metabolic levels. CellChat analysis was applied to investigate the interactions between and different cell types. The relationship between expression and drug concentration was analyzed.
messenger RNA was found to be upregulated in bulk RNA, IHC tissues samples and malignant hepatocytes. The proliferation of JHH2 cell lines was most significantly inhibited after knockdown. In biological pathways, the development of HCC was found to be linked to the regulation of ubiquitin-mediated proteolysis. Additionally, scRNA-seq results indicated that highly expressed was in the G2/M phase, with increased glycolysis/gluconeogenesis activity. A CellChat analysis showed that was associated with the regulation of the migration inhibitory factor-(cluster of differentiation 74 + C-X-C chemokine receptor type 4) pathway. Higher expression correlated with stronger effects of sorafenib, dasatinib, ibrutinib, lapatinib, nilotinib and afatinib.
The high expression level of may regulate the cell cycle and metabolic levels of HCC through the ubiquitination-related pathway, thereby promoting disease progression.
作为肿瘤发展中泛素化的关键调节因子，在肝细胞癌（HCC）中尚未得到充分研究。
阐明其在HCC中的表达及其与泛素化相关的潜在调控机制。
整合批量RNA（RNA测序和微阵列）、免疫组织化学（IHC）组织和单细胞RNA测序（scRNA-seq）数据，全面研究其在HCC中的表达。进行成簇规律间隔短回文重复序列分析，以评估基因敲除后HCC细胞系的生长情况。进行富集分析以探索其功能。利用scRNA-seq数据检查细胞周期和代谢水平。应用CellChat分析研究其与不同细胞类型之间的相互作用。分析其表达与药物浓度之间的关系。
在批量RNA、IHC组织样本和恶性肝细胞中发现信使核糖核酸上调。基因敲低后，JHH2细胞系的增殖受到最显著抑制。在生物途径中，发现HCC的发展与泛素介导的蛋白水解调节有关。此外，scRNA-seq结果表明，高表达处于G2/M期，糖酵解/糖异生活性增加。CellChat分析表明，其与迁移抑制因子-（分化簇74 + C-X-C趋化因子受体4型）途径的调节有关。较高的表达与索拉非尼、达沙替尼、伊布替尼、拉帕替尼、尼洛替尼和阿法替尼的更强作用相关。
其高表达水平可能通过泛素化相关途径调节HCC的细胞周期和代谢水平，从而促进疾病进展。
