Functions of three ubiquitin-conjugating enzyme 2 genes in hepatocellular carcinoma diagnosis and prognosis

BACKGROUND Liver cancer ranks the third cause of cancer-related death worldwide.The most common type of liver cancer is hepatocellular carcinoma(HCC).The survival time for HCC patients is very limited by years due to the lack of efficient treatment,failure of early diagnosis,and poor prognosis.Ubiquitination plays an essential role in the biochemical processes of a variety of cellular functions.AIM To investigate three ubiquitination-associated genes in HCC.METHODS Herein,the expression levels of ubiquitin-conjugating enzymes 2(UBE2)including UBE2C,UBE2T,and UBE2S in tumor samples of HCC patients and nontumor controls at the Cancer Genome Atlas(TCGA)database,was comprehensively analyzed.The relationship of UBE2 gene expression level with cancer stage,prognostic outcome,and TP53 mutant status was studied.RESULTS Our results showed that UBE2C,UBE2T,and UBE2S genes were overexpressed in HCC samples compared to non-tumor tissues.Dependent on the cancer progression stage,three UBE2 genes showed higher expression in tumor tissues at all four stages compared to non-tumor control samples.Furthermore,a significantly higher expression of these genes was found in stage 2 and stage 3 cancers compared to stage 1 cancer.Additionally,overexpression of those genes was negatively associated with prognostic outcome and overall survival time.Patients with TP53 mutation showed a higher expression level of three UBE2 genes,indicating an association between UBE2 expression with p53 function.CONCLUSION In summary,this study shed light on the potential roles of UBE2C,UBE2T,UBE2S on diagnostic and prognostic biomarkers for HCC.Moreover,based on our findings,it is appealing to further explore the correlation of those genes with TP53 mutation in HCC and the related mechanisms.

UBE2C基因在肾透明细胞癌中的临床预后价值及分子机制探究

目的 探讨泛素结合酶E2C(UBE2C)在肾透明细胞癌(KIRC)中的表达模式、临床预后价值以及调节KIRC的分子机制。方法 通过肿瘤基因组图谱数据库(TCGA)和人类蛋白质表达图谱数据库(HPA)分析UBE2C基因在KIRC组织和正常组织中的表达差异。结合KIRC患者的临床信息,利用单因素及多因素Cox回归模型分析UBE2C基因在KIRC患者中的预后价值。通过基因富集分析(GSEA)了解UBE2C基因调控KIRC的分子机制。计算KIRC患者中的浸润免疫细胞含量,并评估UBE2C基因表达水平与免疫细胞浸润含量的相关性。结果 KIRC组织中的UBE2C基因和蛋白表达水平均高于正常肾组织(P<0.05)。KIRC组织中UBE2C表达与肿瘤位置、组织学分级、病理分期及TNM分期有关(P<0.05)。单因素及多因素Cox回归分析结果显示,UBE2C可作为预测KIRC患者总生存期(OS)的独立预后因素(P<0.05)。GSEA结果表明,UBE2C可能参与调节细胞因子-细胞因子受体相互作用、细胞周期检查点、ECM糖蛋白等多条信号通路。UBE2C基因表达水平与KIRC肿瘤微环境中Treg细胞、T细胞、Th17细胞、B细胞、CD8+T细胞和巨噬细胞浸润等显著相关。UBE2C同免疫检查点分子PDCD1(PD1)、CTLA4、CD27、LAG3等表达水平也显著相关。结论 UBE2C可作为KIRC患者的一个风险预后因子,同时UBE2C可能作为KIRC治疗的潜在靶点。

UBE2C regulates proliferation and invasion of neuroblastoma: An experimental study

Objective:To study the regulatory effect of ubiquitin-conjugating enzyme 2C (UBE2C) on the proliferation and invasion of neuroblastoma.Methods: SH-SY5Y neuroblastoma cell lines were cultured and randomly divided into UBE2C-siRNA group and NC-siRNA group that were transfected with UBE2C siRNA and NC siRNA respectively. 24 h after siRNA transfection, the RNA in the cells was extracted, and fluorescence quantitative PCR reaction was used to detect the mRNA expression of pro-proliferation genes YB-1, CyclinD1, CDK4, Aurora-A and Ki-67, anti-proliferation genes LC3, Beclin1, GRP78, IRE1α, PERK and ATF6 as well as invasion genes KLF4, RIPK3, HIF-1α, Integrinβ1 and MMP9.Results: YB-1, CyclinD1, CDK4, Aurora-A, Ki-67, KLF4, RIPK3, HIF-1α, Integrinβ1 and MMP9 mRNA expression in UBE2C-siRNA group of cells were significantly lower than those in NC-siRNA group whereas LC3, Beclin1, GRP78, IRE1α, PERK and ATF6 mRNA expression were significantly higher than those in NC-siRNA group.Conclusions: Inhibition of the UBE2C gene can regulate the expression of proliferation and invasion genes in neuroblastoma to hinder cell proliferation and invasion.

Correlation of KLF4 and UBE2C expression levels in neuroblastoma with cell adhesion and migration

Objective: To study the correlation of KLF4 and UBE2C expression levels in neuroblastoma with cell adhesion and migration. Methods: A total of 56 children who were diagnosed with neuroblastoma in the Central Hospital of Enshi Autonomous Prefecture between May 2014 and February 2017 were selected as the NB group of the study, and the lesion tissue was collected;38 children who were treated in the Central Hospital of Enshi Autonomous Prefecture due to serious hydronephrosis during the same period were selected as the control group of the study, and the normal adrenal gland tissue was collected. The mRNA expression and protein expression of KLF4 and UBE2C as well as the protein expression of cell adhesion molecules and migration molecules in clinical tissue samples were determined. Results: The mRNA expression and protein expression of KLF4 in neuroblastoma tissue of NB group were greatly lower than those of control group whereas the mRNA expression and protein expression of UBE2C were greatly higher than those of control group;PDLIM1, AMF, GPx1, L1CAM, Nrg1, RANK, RANKL, Inβ1, MTA1 and MMP9 protein expression in neuroblastoma tissue of NB group were greatly higher than those of control group, negatively correlated with the protein expression KLF4, and positively correlated with the protein expression of UBE2C. Conclusion: The low expression of KLF4 and the high expression of UBE2C in neuroblastoma can promote the adhesion and migration of tumor cells.

UBE2C affects breast cancer proliferation through the AKT/mTOR signaling pathway

Background:Ubiquitin-conjugating enzyme E2C(UBE2C)has been shown to be associated with the occurrence of various cancers and involved in many tumorigenic processes.This study aimed to investigate the specific molecular mechanism through which UBE2C affects breast cancer(BC)proliferation.Methods:BC-related datasets were screened according to filter criteria in the Gene Expression Omnibus(GEO)database and The Cancer Genome Atlas(TCGA)database.Then differentially expressed genes(DEGs)were identified using Venn diagram analysis.By using DEGs,we conducted the following analyses including Gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG),protein-protein interaction(PPI),and survival analysis,and then validated the function of the hub geneUBE2C using quantitative reverse transcription-polymerase chain reaction(RT-qPCR),cell counting kit-8(CCK-8)assay,transwell assay,and Western blot assay.Results:In total,151 DEGs were identified from the GEO and TCGA databases.The results of GO analysis demonstrated that the DEGs were significantly enriched with mitotic nuclear division,lipid droplet,and organic acid-binding.KEGG analysis showed that the peroxisome proliferators-activated receptor(PPAR)signaling pathway,regulation of lipolysis in adipocytes,and proximal tubule bicarbonate reclamation were significantly enriched in the signal transduction pathway category.The top three hub genes that resulted from the PPI network wereFOXM1,UBE2C,andCDKN3.The results of survival analysis showed a close relationship between UBE2C and BC.The results of CCK-8 and transwell assays suggested that the proliferation and invasion ofUBE2C knockdown cells were significantly inhibited(P<0.050).The results of Western blot assay showed that the level of phosphorylated phosphatase and tensin homology deleted on chromosome 10(p-PTEN)was obviously increased(P<0.050),whereas the levels of phosphorylated protein kinase B(p-AKT),phosphorylated mammalian target of rapamycin(p-mTOR),and hypoxia-inducible factor-1 alpha(HIF-1α)were dramatically decreased(P<0.050)in theUBE2C knockdown cell.Conclusion:UBE2C can promote BC proliferation by activating the AKT/mTOR signaling pathway.