Ubiquitin-conjugating Enzyme E2C Expression Research Articles

Ubiquitin-Conjugating Enzyme E2C Activates Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway to Promote Growth and Migration of Cutaneous Squamous Cell Carcinoma Cells

Cutaneous squamous cell carcinoma is prone to metastasis at its advanced stage. Previous studies reported that the ubiquitin-conjugating enzyme E2C is a proto-oncogene that causes cancer in various tumors. This study aimed to investigate the role of the ubiquitin-conjugating enzyme E2C in cutaneous squamous cell carcinoma. We initially analyzed the expression profile in the gene expression omnibus database. We obtained the intersection genes, established a protein-protein interaction network, and identified ubiquitin-conjugating enzyme E2C as the key gene. Furthermore, microarray data revealed that the ubiquitin-conjugating enzyme E2C expression is elevated in cutaneous squamous cell carcinoma. Ubiquitin-conjugating enzyme E2C overexpression plasmids and siRNA of ubiquitin-conjugating enzyme E2C were transfected into cutaneous squamous cell carcinoma cells to analyze the effects of ubiquitin-conjugating enzyme E2C on cutaneous squamous cell carcinoma cell proliferation, migration, and invasion. The expression of associated proteins was detected using Western blot assay to confirm the impact of the ubiquitin-conjugating enzyme E2C on the phosphatidylinositol-3-kinase/threonine kinase signaling pathway. Ubiquitin-conjugating enzyme E2C knockdown inhibited cutaneous squamous cell carcinoma cell viability, migration, and invasion, and the phosphatidylinositol-3-kinase/threonine kinase signaling pathway, while ubiquitin-conjugating enzyme E2C overexpression had opposite results. In summary, Ubiquitin-conjugating enzyme E2C is a potential therapeutic target for cutaneous squamous cell carcinoma since it encourages the proliferation and migration of cutaneous squamous cell carcinoma cells.

UBE2C promotes malignancy of cutaneous squamous cell carcinoma.

Our study aimed to study the involvement of ubiquitin-conjugating enzyme E2C (UBE2C) in cutaneous squamous cell carcinoma (cSCC). As the second most common malignancy with a rising incidence, understanding the molecular mechanisms driving cSCC is crucial for improved diagnosis and treatment. We combined multiple datasets of cSCC in Gene Expression Omnibus (GEO) repository to investigate its expression and diagnostic value. We collected patient specimens and performed immunohistochemistry to examine its expression in patients and its correlation with tumor histological grade. Moreover, we compared UBE2C expression between cSCC cells and primary human epidermal keratinocytes. Subsequently, we explored the effects of UBE2C inhibition on tumor cell proliferation, migration and apoptosis through CCK8, wound healing, Transwell, and flow cytometry assay. The integrated analysis revealed an upregulation of UBE2C level in cSCC. Immunohistochemistry demonstrated high UBE2C expression was associated with poorer tumor histological grade. Cell experiments further supported the crucial role of UBE2C in promoting the malignant behavior of cSCC cells. Our findings indicate UBE2C is up-regulated in cSCC and contributes to its malignant behavior. These results suggest UBE2C has the potential to serve as both a cSCC biomarker and a therapeutic target.

Comprehensive analysis of UBE2C expression and its potential roles and mechanisms in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) ranks one of the most common and lethal cancers all over the world. Previous studies suggest that ubiquitin-conjugating enzyme E2C (UBE2C) serves as an oncogene in human cancers. However, its expression, diagnosis, prognosis and potential mechanisms in HCC remain largely unknown. In this study, the expression of UBE2C in HCC was first analyzed by comprehensive bioinformatic analysis. ROC curve analysis and survival analysis were employed to assess the diagnostic and prognostic roles of UBE2C in HCC. UBE2C promoter methylation level and upstream regulatory miRNAs of UBE2C in HCC were explored. The present work demonstrated that UBE2C was significantly upregulated in HCC compared with normal controls. We also found significant diagnostic and prognostic values of UBE2C in HCC. Promoter methylation of UBE2C was obviously decreased in HCC and was negatively correlated with UBE2C mRNA expression. 10 miRNAs were predicted to potentially bind to UBE2C. In vitro assay and bioinformatic correlation analysis together revealed that hsa-miR-193b-3p might be another key upstream regulatory mechanism of UBE2C in HCC. In conclusion, UBE2C is overexpressed in HCC and may serve as a key diagnostic/prognostic biomarker for patients with HCC.

Validation of a Disease-Free Survival Prediction Model Using UBE2C and Clinical Indicators in Breast Cancer Patients.

To explore the validation of a disease-free survival (DFS) model for predicting disease progression based on the combination of ubiquitin-conjugating enzyme E2 C (UBE2C) levels and clinical indicators in breast cancer patients. We enrolled 121 patients with breast cancer, collected their baseline characteristics and follow-up data, and analyzed the UBE2C levels in tumor tissues. We studied the relationship between UBE2C expression in tumor tissues and disease progression events of patients. We used the Kaplan-Meier method for identifying the disease-free survival rate of patients, and the multivariate Cox regression analysis to study the risk factors affecting the prognosis of patients. We sought to develop and validate a model for predicting disease progression. We found that the level of expression of UBE2C could effectively distinguish the prognosis of patients. In the Receiver Operating Characteristic (ROC) curve analysis, the Area under the ROC Curve (AUC) = 0.826 (0.714-0.938) indicating that high levels of UBE2C was a high-risk factor for poor prognosis. After evaluating different models using the ROC curve, Concordance index (C-index), calibration curve, Net Reclassification Index (NRI), Integrated Discrimination Improvement Index (IDI), and other methods, we finally developed a model for the expression of Tumor-Node (TN) staging using Ki-67 and UBE2C, which had an AUC=0.870, 95% CI of 0.786-0.953. The traditional TN model had an AUC=0.717, and 95% CI of 0.581-0.853. Decision Curve Analysis (DCA) and Clinical Impact Curve (CIC) analysis indicated that the model had good clinical benefits and it was relatively simple to use. We found that high levels of UBE2C was a high-risk factor for poor prognosis. The use of UBE2C in addition to other breast cancer-related indicators effectively predicted the possible disease progression, thus providing a reliable basis for clinical decision-making.

UBE2C-mediated Autophagy Inhibition via Ubiquitination of SIRT1 Contributes to Endometrial Cancer Progression.

Our study highlights the tumorigenic role and regulatory mechanism of UBE2C in endometrial cancer; UBE2C inhibits endometrial cancer cell apoptosis through autophagy-related mechanisms and our findings provide new insights into the treatment of endometrial cancer.

Ceramide synthase 6 antisense RNA 1 contributes to the progression of breast cancer by sponging miR-16-5p to upregulate ubiquitin-conjugating enzyme E2C.

Breast cancer (BC) is the most dangerous female mortality all over the world, described by unavoidable spread and metastaticity of BC cells. Increasing evidences verified that lncRNA play a major role in the tumorgenesis and development of BC cell. The purpose of this study is to investigate the roles of lncRNA ceramide synthase 6 antisense RNA 1 (CERS6-AS1) and ubiquitin-conjugating enzyme E2C (UBE2C) in BC and explore the regulatory association among miR-16-5p, CERS6-AS1, and UBE2C in BC. The CERS6-AS1 and UBE2C expression levels were determined by real time quantitative PCR in cell lines and tissues of BC. The function of CERS6-AS1 and UBE2C in the apoptosis, proliferation, and migration was confirmed by cell counting kit-8, Transwell, and flowcytometry tests. We performed tumor xenograft assay to validate the roles of CERS6-AS1 in vivo. The expression of UBE2C proteins was evaluated by Western Blot analysis. Moreover, the relationship among UBE2C, CERS6-AS1, and miR-16-5p was verified by luciferase report assay. It was found that CERS6-AS1 and UBE2C were meaningfully upregulated in BC, and knockdown of both CERS6-AS1 and UBE2C inhibited the BC cell proliferation and migration, whereas induced apoptosis. Mechanistically, CERS6-AS1 could facilitate BC progression by sponging miR-16-5p for upregulation of the UBE2C expression. The CERS6-AS1/miR-16-5p/UBE2C axis might be a prospective therapeutic target in the BC treatment by sponging miR-16-5p to upregulate UBE2C, which might contribute to the development of BC.

UBE2C mediated radiotherapy resistance of head and neck squamous cell carcinoma by regulating oxidative-stress-relative apoptosis.

Purpose: Radiotherapy resistance is the main obstacle in the effective treatment of advanced head and neck squamous cell carcinoma (HNSCC). Increasing scientific opinions present that ubiquitin-conjugating enzyme E2C (UBE2C) might be a target gene acting as an oncogene.Method: TCGA database was used to analyze the expression of UBE2C in HNSCC patients, and the relationship between UBE2C expression and prognosis. Western blot and RT-PCR were used to assess UBE2C expression before and after radiation. Then, cell viability experiment and colony formation were used to evaluate proliferation after 2 Gy radiation. Cell viability experiment, migration, and invasion were evaluated in the condition of UBE2C knock-down. Western blot and RT-PCR were used to assess the expression of apoptosis and ROS relative gene expression. Then, the xenograft model was used to evaluate the efficacy of radiation combined with UBE2C suppression.Result: The expression of UBE2C was high in tumors of patients with HNSCC and relatives with poor prognoses. Si-UBE2C cells showed proliferation inhibited and apoptosis enhanced after radiation. Furthermore, the mechanism of UBE2C in HNSCC radioresistance was explored. We performed RT-PCR to find the 4-HNE, which increases oxidative-stress-relative apoptosis in Si-UBE2C cells after radiation.Conclusions: Through the RT-PCR, WB, cell viability experiment, migration, invasion, and in vivo experiment, UBE2C was confirmed to downregulate oxidative-stress-relative apoptosis induced by radiation and promote the development of malignant tumor cells.

UBE2C promotes the progression of pancreatic cancer and glycolytic activity via EGFR stabilization-mediated PI3K-Akt pathway activation.

Pancreatic cancer (PC) is among the most prevalent and deadliest endocrine tumors, yet the mechanisms governing its pathogenesis remain to be fully clarified. While ubiquitin-conjugating enzyme E2C (UBE2C) has been identified as an important oncogene in several cancers, its importance in PC has yet to be established. UBE2C expression in PC tumor samples and cell lines was examined via quantitative real-time polymerase chain reaction (qRT-PCR), while appropriate commercial kits were used to assess lactate production, ATP generation, and the uptake of glucose. UBE2C was found to be upregulated in PC patient tumors and correlated with poorer survival outcomes. In PC cell lines, the silencing of this gene suppressed the malignant activity of cells, thus supporting its identification as an oncogene in this cancer type. Mechanistically, UBE2C was found to promote enhanced matrix metalloproteinase (MMP) protein expression via activating the PI3K-Akt pathway. Moreover, it was found to bind to the epidermal growth factor receptor (EGFR), stabilizing it and driving additional PI3K-Akt pathway activation. UBE2C knockdown in PC cells impaired their uptake of glucose and their ability to produce lactate and ATP. In conclusion, the results of this study support a role for UBE2C as a driver of metastatic PC progression owing to its ability to bind to EGFR and to induce signaling via the PI3K-Akt pathway.

Pan-Cancer Analyses of the Tumor Microenvironment Reveal That Ubiquitin-Conjugating Enzyme E2C Might Be a Potential Immunotherapy Target.

Increasing evidence indicated that the tumor microenvironment (TME) played a crucial role in cancer initiation and progression. Ubiquitin-conjugating enzyme E2C (UBE2C) was differentially expressed in many cancer types. However, the immunological and prognostic roles of UBE2C were unclear. Differentially expressed genes (DEGs) of 29 cancer types were downloaded from GEPIA2 and 4 cancer types failed to download owing to no DEGs. Furthermore, the gene expression profiles, mutation data, and survival data of 33 cancer types were obtained from UCSC Xena. Clinical stage relevance, tumor mutational burden (TMB), TME relevance analysis, and gene set enrichment analysis (GSEA) of DEGs in 33 cancer types were performed. And DEGs were identified in oral squamous cell carcinoma (OSCC) by biological experiments. Previous studies indicated that UBE2C was related to the prognosis of many cancers. In our study, the higher UBE2C expression level meant a terminal clinical stage in 8 cancer types and the expression level of UBE2C was related to TMB in 20 cancer types. In addition, both immune relevance analysis and GSEA showed that UBE2C might participate in immune response in many cancers. Furthermore, the UBE2C mRNA level and protein level were all identified as upregulated in OSCC cell lines and tissues. UBE2C was differentially expressed in many cancer types and related to the pathogenesis and TME of many cancers, which might be a potential diagnostic and therapeutic biomarker.

Overexpression of UBE2C in esophageal squamous cell carcinoma tissues and molecular analysis

BackgroundEsophageal cancer is a common malignant tumor and its 5-year survival rate is much lower than 30% due to its invasiveness and pronounced metastasis ability, as well as the difficulty in early diagnosis. This study aimed to elucidate the molecular mechanism of ubiquitin conjugating enzyme E2 C (UBE2C) in esophageal squamous cell carcinoma (ESCC).MethodsIn this study, we conducted a comprehensive evaluation of the UBE2C expression in ESCC by collecting the protein and mRNA expression data (including in-house RNA-seq, in-hosue immunohistochemistry, TCGA-GTEx RNA-seq and tissue microarray) to calculate a combined standardized mean difference (SMD) and summary receiver operating characteristic curve (sROC). Kaplan-Meier (K-M) method was used for survival analysis. We also explored the mechanism of UBE2C in ESCC by combing the differentially expressed genes (DEGs) of ESCC, related-genes of UBE2C in ESCC and the putative miRNAs and lncRNAs which may regulate UBE2C.ResultsUBE2C protein and mRNA were highly expressed in ESCC tissues (including 772 ESCC tissue samples and 1837 non-cancerous tissue control samples). The pooled SMD of UBE2C expression values was 1.98 (95% CI: 1.51–2.45, p < 0.001), and the the area under the curve (AUC) of the sROC was 0.93 (95% CI: 0.90–0.95). The results of survival analysis suggested that UBE2C is likely to play different roles in different stages of the ESCC. Pathway anaylsis showed that UBE2C mainly influenced the biological function of esophageal cancer by synergistic effects with CDK1, PTTG1 and SKP2. We also constructed a potential UBE2C-related ceRNA network for ESCC (HCP5/has-miR-139-5p/UBE2C).ConclusionUBE2C mRNA and protein level were highly expressed in ESCC and UBE2C was likely to play different roles in different stages of the ESCC.

The Relationship Between UBE2C and AGGF1 Overexpression and Tumor Angiogenesis in Non-Small Cell Lung Cancer.

BackgroundTumor infiltration and metastasis are the leading causes of death for patients with tumors. Angiogenesis is a prerequisite for tumor growth and metastasis. Angiogenic factor with G patch and FHA domains 1 (AGGF1) is an angiogenic factor, whereas ubiquitin-conjugating enzyme E2C (UBE2C) functions in protein ubiquitination. Microvessel density (MVD) is the most common indicator of tumor microvessels, and vasculogenic mimicry (VM) facilitates blood supply to tumors. This study explored UBE2C and AGGF1 expression in non-small cell lung cancer (NSCLC) and their relationship with angiogenesis and prognosis to identify biological factors that might predict NSCLC infiltration, metastasis, and prognosis.MethodsThe specimens and clinical pathological data of patients with NSCLC confirmed by pathology after surgical resection between January 2013 and December 2015 were collected. UBE2C and AGGF1 expression, as well as microvessel formation and VM in NSCLC, was observed using immunohistochemistry. The relationships between UBE2C, AGGF1, MVD, VM, and clinical pathological parameters and their relationships with overall survival (OS) and disease-free survival (DFS) were analyzed.ResultsUBE2C and AGGF1 levels in NSCLC tissues were significantly higher than those in corresponding normal tissues (57.1% vs 15.6 and 59.7% vs 25.3%, respectively; P < 0.05). UBE2C, AGGF1, MVD, and VM were positively correlated with each other (P < 0.05) and were all related to tumor size, lymph node metastasis, and tumor-node-metastasis stage (P < 0.05). Kaplan–Meier analysis showed that patient OS and DFS in the UBE2C, AGGF1, VM-positive, and high-MVD groups were reduced (all P < 0.001). Univariate and multivariate analyses showed that UBE2C, AGGF1, VM, and MVD were independent risk factors for NSCLC prognosis.ConclusionUBE2C and AGGF1 overexpression is associated with angiogenesis and poor prognosis and may be important for predicting NSCLC invasion, metastasis, and prognosis.

Ubiquitin Conjugating Enzyme E2C Correlates with Tumor Microenvironment and Impacts with Patient Prognosis: A Pan-Cancer Analysis

Background: Increasing evidences indicated that tumor microenvironment played a crucial role in cancer initiation and progression. Ubiquitin-conjugating enzyme E2C(UBE2C) was differentially expressed in 33 cancer types. However, the immunological and prognostic roles ofUBE2C across 33 cancers were unclear. Methods: Differentially expressed genes(DEGs) of 29 cancer types were downloaded from GEPIA2 and 4 cancer types were excluded. Furthermore, the gene expression profiles, mutation data and survival data of 33 cancer types were obtained from UCSC Xena. Survival and prognostic analysis, clinical stage relevance, tumor mutational burden(TMB) and tumor microenvironment(TME) relevance analysis and Gene set enrichment analysis(GSEA) of DEGs in 33 cancer types were performed. Findings: UBE2C was identified as the only one DEG in 33 cancer types which was related to Overall survival(OS) in 13 cancer types, disease-specific survival(DSS) in 8 cancer types, disease-free survival(DFS) in 11 cancer types and progression-free survival(PFS) in 14 cancer types. In addition, the higher UBE2C expression level meant terminal clinical stage in 8 cancer types and the expression level of UBE2C was related to TMB in 20 cancer types. Finally, both immune relevance analysis and GSEA indicated that UBE2C played a vital role in immune response of many cancers. Interpretation:UBE2C was differentially expressed in 33 cancer types and related to the pathnogenesis and tumor microenvironment of many cancers, which might be a potential diagnostic and therapeutic biomarker. Funding: This work was supported by the National Natural Science Foundation of China (81472536); the Science and Technology Planning Project of Guangdong Province (2017A020215181;2014A020212440); Project of Educational Commission of Guangdong Province of China (2018KTSCX026); the Scientific Research Planning Project of Southern Medical University (CX2018N016) and the Presidential Foundation of the Nanfang Hospital (2014027;2019Z030). Declaration of Interest: None Ethical Approval: The Nanfang Hospital ethics committee (AF/SC-09/03.2) approved this study.

UBE2C mRNA expression controlled by miR-300 and HuR determines its oncogenic role in gastric cancer

Ubiquitin Conjugating Enzyme E2 C (UBE2C) has a key oncogenic role in many human malignancies, including gastric cancer. However, it remains largely unknow at which level UBE2C expression is altered, as well as what are the downstream targets of UBE2C. In this study, we show that UBE2C is frequently overexpressed in gastric cancer patients. Interestingly, high expression of UBE2C mRNA instead of genome amplification is the predominant alterations observed in both stomach adenocarcinoma. We then confirmed that silencing UBE2C not only suppresses gastric cancer colony formation, but also inhibits DNA biosynthesis. Furthermore, we discovered that microRNA-300 is able to suppress gastric cancer progression through reducing UBE2C mRNA abundance, which is protected by an RNA binding protein HuR. Lastly, through an analysis of genes whose expressions correlate with that of UBE2C from gastric cancer cell lines, we have proposed several key genes that can be regulated by UBE2C, contributing to its oncogenic activity.

Identification of hub genes involved in the occurrence and development of hepatocellular carcinoma via bioinformatics analysis.

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy, which is a major cause of cancer morbidity and mortality worldwide. Thus, the aim of the present study was to identify the hub genes and underlying pathways of HCC via bioinformatics analyses. The present study screened three datasets, including GSE112790, GSE84402 and GSE74656 from the Gene Expression Omnibus (GEO) database, and downloaded the RNA-sequencing of HCC from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) in both the GEO and TCGA datasets were filtered, and the screened DEGs were subsequently analyzed for functional enrichment pathways. A protein-protein interaction (PPI) network was constructed, and hub genes were further screened to create the Kaplan-Meier curve using cBioPortal. The expression levels of hub genes were then validated in different datasets using the Oncomine database. In addition, associations between expression and tumor grade, hepatitis virus infection status, satellites and vascular invasion were assessed. A total of 126 DEGs were identified, containing 70 upregulated genes and 56 downregulated genes from the GEO and TCGA databases. By constructing the PPI network, the present study identified hub genes, including cyclin B1 (CCNB1), cell-division cycle protein 20 (CDC20), cyclin-dependent kinase 1, BUB1 mitotic checkpoint serine/threonine kinase β (BUB1B), cyclin A2, nucleolar and spindle associated protein 1, ubiquitin-conjugating enzyme E2 C (UBE2C) and ZW10 interactor. Furthermore, upregulated CCNB1, CDC20, BUB1B and UBE2C expression levels indicated worse disease-free and overall survival. Moreover, a meta-analysis of tumor and healthy tissues in the Oncomine database demonstrated that BUB1B and UBE2C were highly expressed in HCC. The present study also analyzed the data of HCC in TCGA database using univariate and multivariate Cox analyses, and demonstrated that BUB1B and UBE2C may be used as independent prognostic factors. In conclusion, the present study identified several genes and the signaling pathways that were associated with tumorigenesis using bioinformatics analyses, which could be potential targets for the diagnosis and treatment of HCC.

Combining Bioinformatics and Experiments to Identify and Verify Key Genes with Prognostic Values in Endometrial Carcinoma.

Endometrial carcinoma(EC) is the most common cancer of female reproductive system, thus requiring for new effective biomarkers which could predict the onset of EC and poor prognosis. Our study integrated two GEO datasets(i.e.GSE63678, GSE17025) and TCGA(The Cancer Genome Atlas ) UCEC data to screen out 344 common differentially expressed genes(DEGs), which were further analyzed by GO(gene ontology) functions and KEGG(Kyoto Encyclopedia of Gene and Genome) pathways. KEGG analysis results showed these DEGs were mainly enriched in cell cycle, oocyte meiosis, cellular senescence, carbon metabolism and p53 signaling pathway. Top 20 hub genes with higher degree were selected from PPI(protein-protein interaction) network and 15 of them were associated with the prognosis of EC, that is, CCNB2, CDC20, BUB1B, UBE2C, AURKB, FOXM1, NCAPG, RRM2, TPX2, DLGAP5, CDCA8, CDC45, MKI67, BUB1, KIF2C. UBE2C(Ubiquitin Conjugating Enzyme E2 C) was chosen for further validation in TCGA cohort on mRNA level and in our patient samples on protein level by immunohistochemistry. UBE2C was significantly highly expressed in endometrial carcinoma, and its expression level was associated with advanced FIGO staging and poor prognosis. Cox risk model demonstrated high UBE2C expression was an independent risk factor. Somatic mutations, elevated copy number, DNA hypomethylation all contributed to its overexpression. Therefore, by combination of bioinformatics and experiment, our study provided a unique insight into the pathogenesis and molecular mechanisms underlying EC and discovered new biomarkers for early diagnosis and prognostic prediction. UBE2C could serve as a potential marker to predict poor prognosis and as a therapeutic target.

Depletion of UBE2C reduces ovarian cancer malignancy and reverses cisplatin resistance via downregulating CDK1

Ovarian cancer is the most lethal gynecological malignancy, but the mechanisms of ovarian cancer progression and cisplatin resistance remain unclear. Emerging evidence suggested that ubiquitin-conjugating enzyme E2C (UBE2C) was highly expressed in a variety of tumors and acted as an oncogene. In our study, we demonstrated that UBE2C was overexpressed in ovarian cancer by immunohistochemistry (IHC) and The Cancer Genome Atlas (TCGA) database analysis. It was also found that high levels of UBE2C expression predicted worse clinical outcomes in ovarian cancer. After knocking down UBE2C, SKOV3 and A2780 cells showed inhibitory cell proliferation, increased apoptosis by blocking G2/M transition in vitro and in vivo. Besides, the downregulation of UBE2C reversed the cisplatin resistance states of SKOV3/DDP and A2780/DDP cells. Interestingly, CDK1 expression was also downregulated in UBE2C depleted ovarian cancer cells. Furthermore, we found that UBE2C expression was highly correlated with CDK1 expression in ovarian cancer tissues and cell lines, indicating that UBE2C might cooperate with CDK1 in ovarian tumorigenesis. Collectively, our findings strongly supported UBE2C as a candidate oncogene and a potential target for the treatment of ovarian cancer.

The expression of ubiquitin-conjugating enzyme E2C and KAI1 in ovarian carcinoma and their clinical significance.

Ubiquitin-conjugating enzyme E2C (UBE2C) is considered to play an important role in the tumorigenesis of many cancers and promote cell cycle progression. Kangai 1 (KAI1) is considered as a suppressor gene of tumor metastasis. However, the clinicopathological significance and their each relationship of UBE2C and KAI1 in epithelial ovarian carcinoma (EOC) are not widely reported. The purpose of this study is to detect the expression of UBE2C and KAI1 in EOC and their clinical significance.The expression of UBE2C and KAI1 in 180 cases of EOC tissues, 60 cases of normal ovarian epithelial tissues, and 60 cases of ovarian benign tumor tissues were detected by immunohistochemistry. Patients data were also collected.Positive expression of UBE2C in EOC (38.9%) was significantly higher than that both in the normal group (0%) and benign tumors group (10.0%). Furthermore, the expression of UBE2C was positively associated with grades of differentiation, implants, lymph node metastasis (LNM), as well as the International Federation of Gynecology and Obstetrics (FIGO) stages. Positive expression of KAI1 in EOC (25.0%) was significantly lower than that both in the normal group (100%) and benign tumors group (75.0%). And the expression of KAI1 was inversely associated with grades of differentiation, implants, LNM, and FIGO stages. Kaplan–Meier survival analyses demonstrated that UBE2C positive expression for patients with EOC had unfavorably overall survival (OS) time when compared with negative UBE2C for patients. And KAI1 positive expression for patients had favorably OS time when compared with negative KAI1 for patients. Multivariate analysis showed that positive expression of UBE2C and KAI1, implants, and FIGO stages were considered as independently prognostic factors for OS in patients with EOC. Moreover, UBE2C expression was significantly higher in high grade serous adenocarcinoma (SA) when compared with low grade SA; and KAI1 expression was significantly lower in high grade SA when compared with low grade SA. High grade SA patients had higher rates of implants, LNM, and high FIGO stages when compared with low grade SA. High grade SA patients had unfavorably OS time when compared with low grade SA.UBE2C and KAI1 should be considered as potential biomarkers of EOC prognosis.

Anticancer effect of icaritin on prostate cancer via regulating miR-381-3p and its target gene UBE2C.

Prostate cancer (PCa) is one of the most common health‐related issues in the male individuals of western countries. Icaritin (ICT) is a traditional Chinese herbal medicine that exhibits antitumor efficacy in variety of cancers including PCa. However, the precise function and detailed molecular mechanism of ICT in the regression of PCa remain unclear. Ubiquitin‐conjugating enzyme E2C (UBE2C) is an anaphase‐promoting complex/cyclosome (APC/C)‐specific ubiquitin conjugating enzyme, which acts as an oncogene in PCa progression. The function of ICT in PCa was investigated in transgenic adenocarcinoma mouse prostate (TRAMP) mice using survival analysis, hematoxylin and eosin (HE) staining, TUNEL assay, and immunohistochemistry and in human PCa cell lines using various molecular techniques and functional assays including plasmid construction and transfection. Bioinformatic analyses were performed to identify the interaction between miRNA and UBE2C via the TargetScan algorithm. We demonstrated that ICT inhibited the development and progression of PCa in TRAMP mice by improving the survival rate and tumor differentiation. Furthermore, we found that ICT could significantly inhibit cell proliferation and invasion and induce apoptosis in PCa cells. Consistently, downregulation of UBE2C suppressed the proliferation and invasion of PCa cells. Moreover, a luciferase reporter assay confirmed that UBE2C was a direct target of miR‐381‐3p. Meanwhile, ICT simultaneously downregulated UBE2C expression and upregulated miR‐381‐3p levels in human PCa cells. Altogether, our findings provide a strong rationale for the clinical application of ICT as a potential oncotherapeutic agent against PCa via a novel molecular mechanism of regulating the miR‐381‐3p/UBE2C pathway.

A Comprehensive Bioinformatics Analysis of UBE2C in Cancers.

Ubiquitination is one of the main post-translational modification of proteins. It plays key roles in a broad range of cellular functions, including protein degradation, protein interactions, and subcellular location. In the ubiquitination system, different proteins are involved and their dysregulation can lead to various human diseases, including cancers. By using data available from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases, we here show that the ubiquitin conjugating enzyme, E2C (UBE2C), is overexpressed in all 27 cancers we investigated. UBE2C expression is significantly higher in late-stage tumors, which might indicate its involvement in tumor progression and invasion. This study also revealed that patients with higher UBE2C levels showed a shorter overall survival (OS) time and worse OS prognosis. Moreover, our data show that UBE2C higher-expression leads to worse disease-free survival prognosis (DFS), indicating that UBE2C overexpression correlates with poor clinical outcomes. We also identified genes with positive correlations with UBE2C in several cancers. We found a number of poorly studied genes (family with sequence similarity 72-member D, FAM72D; meiotic nuclear divisions 1, MND1; mitochondrial fission regulator 2, MTFR2; and POC1 centriolar protein A, POC1A) whose expression correlates with UBE2C. These genes might be considered as new targets for cancers therapies since they showed overexpression in several cancers and correlate with worse OS prognosis.

UBE2C functions as a potential oncogene by enhancing cell proliferation, migration, invasion, and drug resistance in hepatocellular carcinoma cells

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Recently, ubiquitin-conjugating enzyme E2C (UBE2C) has been reported to be overexpressed in human cancers and act as a potential oncogene. However, little is known about the functional roles of UBE2C in HCC progression. In the present study, analysis of UBE2C mRNA expression in The Cancer Genome Atlas (TCGA) dataset reveals that significantly higher UBE2C mRNA levels was found in HCC tissues and associated with higher HCC grade. Elevated UBE2C mRNA levels in HCC indicated worsened survival probabilities. Through performing loss-of-function assays, we demonstrated that knockdown of UBE2C expression obviously suppressed proliferation, migration, and invasion of HCC cells in vitro. Moreover, HCC cells with UBE2C knockdown showed higher sensitivity for the treatment of chemotherapeutic drug, including adriamycin (ADR) and 5-fluorouracil (5-FU). Silencing of UBE2C also increased the sensitivity of HCC cells to sorafenib, an approved treatment for patients with advanced-stage HCC. Our findings strongly suggest that UBE2C emerges as a marker for prognosis in HCC, and blocking UBE2C may be a novel strategy for HCC therapies.