BACKGROUND ANAPC1,a key regulator of the ubiquitination in tumour development,has not been thoroughly studied in hepatocellular carcinoma(HCC).AIM To elucidate the expression of ANAPC1 in HCC and its potential regulat...BACKGROUND ANAPC1,a key regulator of the ubiquitination in tumour development,has not been thoroughly studied in hepatocellular carcinoma(HCC).AIM To elucidate the expression of ANAPC1 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 ANAPC1 expression in HCC.Clustered regularly interspaced short palindromic repeats analysis was performed to assess growth in HCC cell lines following ANAPC1 knockout.Enrichment analyses were conducted to explore the functions of ANAPC1.ScRNA-seq data was used to examine the cell cycle and metabolic levels.CellChat analysis was applied to investigate the interactions between ANAPC1 and different cell types.The relationship between ANAPC1 expression and drug concentration was analyzed.RESULTS ANAPC1 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 ANAPC1 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 ANAPC1 was in the G2/M phase,with increased glycolysis/gluconeogenesis activity.A CellChat analysis showed that ANAPC1 was associated with the regulation of the migration inhibitory factor-(cluster of differentiation 74+C-X-C chemokine receptor type 4)pathway.Higher ANAPC1 expression correlated with stronger effects of sorafenib,dasatinib,ibrutinib,lapatinib,nilotinib and afatinib.CONCLUSION The high expression level of ANAPC1 may regulate the cell cycle and metabolic levels of HCC through the ubiquitination-related pathway,thereby promoting disease progression.展开更多
基金Co-first authors:Yu-Xing Tang 0000-0003-4382-4942Co-first authors:Wei-Zi Wu+8 种基金Corresponding author:Gang Chen,MD,Professor,Department of Pathology,The First Affiliated Hospital of Guangxi Medical University,No.6 Shuangyong Road,Nanning 530021,Guangxi Zhuang Autonomous Region,China.chengang@gxmu.edu.cn,0000-0003-2402-2987Co-corresponding authors:Yan-Ting ZhanSheng-Sheng Zhou,0000-0003-2414-460XDa-Tong Zeng,0000-0002-3338-4122Guang-Cai Zheng,0009-0001-5921-6688Rong-Quan He,0000-0002-7752-2080Di-Yuan Qin,0009-0003-3214-4762Wan-Ying Huang,0000-0002-8314-5963Yu-Lu Tang,0009-0004-0462-618X。
文摘BACKGROUND ANAPC1,a key regulator of the ubiquitination in tumour development,has not been thoroughly studied in hepatocellular carcinoma(HCC).AIM To elucidate the expression of ANAPC1 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 ANAPC1 expression in HCC.Clustered regularly interspaced short palindromic repeats analysis was performed to assess growth in HCC cell lines following ANAPC1 knockout.Enrichment analyses were conducted to explore the functions of ANAPC1.ScRNA-seq data was used to examine the cell cycle and metabolic levels.CellChat analysis was applied to investigate the interactions between ANAPC1 and different cell types.The relationship between ANAPC1 expression and drug concentration was analyzed.RESULTS ANAPC1 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 ANAPC1 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 ANAPC1 was in the G2/M phase,with increased glycolysis/gluconeogenesis activity.A CellChat analysis showed that ANAPC1 was associated with the regulation of the migration inhibitory factor-(cluster of differentiation 74+C-X-C chemokine receptor type 4)pathway.Higher ANAPC1 expression correlated with stronger effects of sorafenib,dasatinib,ibrutinib,lapatinib,nilotinib and afatinib.CONCLUSION The high expression level of ANAPC1 may regulate the cell cycle and metabolic levels of HCC through the ubiquitination-related pathway,thereby promoting disease progression.
