Exploring the potential function of high expression of in regulating ubiquitination in hepatocellular carcinoma.

Background: , a key regulator of the ubiquitination in tumour development, has not been thoroughly studied in hepatocellular carcinoma (HCC).

Aim: To elucidate the expression of in HCC and its potential regulatory mechanism related to ubiquitination.

Methods: 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.

Results: 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.

Conclusion: The high expression level of may regulate the cell cycle and metabolic levels of HCC through the ubiquitination-related pathway, thereby promoting disease progression.