Expression Of Ubiquitin-conjugating Enzyme E2T Research Articles

Prognostic Value of UBE2T and Its Correlation with Immune Infiltrates in Lung Adenocarcinoma.

Non-small cell lung cancer has a subtype with a high morbidity and mortality rate called lung adenocarcinoma (LUAD). It is critical to locate reliable prognostic biomarkers for LUAD at this time. Ubiquitin-conjugating enzyme E2T (UBE2T) has been found in numerous malignancies; however, its expression level and potential functions in LUAD are not completely understood at this time. A differentially expressed gene (DEG) screening method was used to identify genes that were expressed differently in 516 samples from LUAD and 59 samples from TCGA datasets. Clinicopathological markers were correlated with UBE2T expression. Using the Kaplan–Meier plotter database, UBE2T was evaluated for its prognostic value in the context of LUAD. In order to examine the importance of independent prognostic factors, both univariable and multivariable Cox regression models were applied. TIMER and CIBERSORT were utilized in order to investigate the connection that exists between UBE2T expression and tumor-infiltrating immune cells. This study collected 578 DEGs in total, as follows: 171 genes were significantly increased, while 408 genes were significantly decreased. We identified 9 survival-related DEGs in LUAD, including ASF1B, CA9, CCNB2, CCNE1, RRM2, SAPCD2, TCN1, TPX2, and UBE2T. Our attention focused on UBE2T, which was highly expressed in LUAD. A correlation was also found between high UBE2T expression and gender, age, advanced clinical stage, and decreased overall survival. In addition, multivariate analysis demonstrated UBE2T expression to be a significant independent diagnostic factor for patients suffering from LUAD. UBE2T was positively correlated with resting T cell CD4+ memory, myeloid dendritic cell resting, mast cell activated, macrophage M2, and B cell plasma, whereas it was negatively correlated with resting T cell CD4+ memory, MDC resting, MDC activated, macrophage M2, and B cell plasma. Overall, high expression levels of UBE2T correlated with poor overall survival in patients with LUAD, and UBE2T was an independent predictor involved in immune infiltration of LUAD. These findings offer fresh perspectives that contribute to our comprehension of the evolution of LUAD.

Circ_0000291 contributes to hepatocellular carcinoma tumorigenesis by binding to miR-1322 to up-regulate UBE2T

Introduction and objectivesCircular RNAs (circRNAs) are identified to show important regulatory functions in cancer biology. We attempted to analyze the role of circ_0000291 in hepatocellular carcinoma (HCC) progression and its related mechanism. MethodsThe circular characteristic of circ_0000291 was tested using exonuclease RNase R. Cell proliferation was analyzed by 5-Ethynyl-2’-deoxyuridine (EdU) incorporation and colony formation assays. Cell apoptosis was measured by flow cytometry and a caspase 3 activity assay kit. Transwell assays were performed to analyze cell migration and invasion abilities. Sphere formation assay was conducted to analyze cell stemness. Dual-luciferase reporter and RNA-pull down assays were conducted to verify the interaction between microRNA-1322 (miR-1322) and circ_0000291 or ubiquitin conjugating enzyme E2 T (UBE2T). ResultsCirc_0000291 was markedly up-regulated in HCC tissues and cell lines. HCC patients with high expression of circ_0000291 displayed a low survival rate. Circ_0000291 knockdown restrained the proliferation, migration, invasion, and stemness and induced the apoptosis of HCC cells. Circ_0000291 directly interacted with miR-1322 and negatively regulated miR-1322 expression. Circ_0000291 knockdown-mediated anti-tumor impacts in HCC cells were largely overturned by the interference of miR-1322. miR-1322 directly paired with the 3’ untranslated region (3’UTR) of UBE2T, and UBE2T was negatively regulated by miR-1322. UBE2T overexpression largely reversed circ_0000291 silencing-induced effects in HCC cells. Circ_0000291 positively regulated UBE2T expression by absorbing miR-1322 in HCC cells. Circ_0000291 silencing notably reduced the tumorigenic potential in vivo. ConclusionCirc_0000291 facilitated HCC progression by targeting miR-1322/UBE2T axis, which provided novel potential biomarkers and targets for HCC patients.

PD01-05 MIR-182-5P INHIBITS THE TUMORIGENESIS OF CLEAR CELL RENAL CELL CARCINOMA BY REPRESSING UBE2T

You have accessJournal of UrologyCME1 May 2022PD01-05 MIR-182-5P INHIBITS THE TUMORIGENESIS OF CLEAR CELL RENAL CELL CARCINOMA BY REPRESSING UBE2T Wu Yucai, Gong Yanqing, Li Xuesong, and Zhou Liqun Wu YucaiWu Yucai More articles by this author , Gong YanqingGong Yanqing More articles by this author , Li XuesongLi Xuesong More articles by this author , and Zhou LiqunZhou Liqun More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002516.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Ubiquitin-conjugating enzyme E2T (UBE2T), a member of the E2 family, has been reported to be overexpressed in certain tumor types and to have an important role in the Fanconi anemia pathway. However, the role of UBE2T in clear cell renal cell carcinoma (ccRCC) has not been clarified. MicroRNAs (miRNAs) participate in tumorigenesis by binding to genes and proteins that regulate cell proliferation or cell apoptosis. The aim of this study was to determine the role of UBE2T and the relationship between miR-182-5p and UBE2T in ccRCC. METHODS: UBE2T expression levels were detected by real-time quantitative PCR (RT-qPCR) and western blot in ccRCC cell lines and tissues. Protein expression of UBE2T was assessed in a total of 93 ccRCC patients from Peking University First Hospital (PKU) by immunohistochemistry (IHC). The effects of UBE2T knockdown/overexpression on the proliferation, invasion and metastasis of ccRCC cells were assessed by MTS assays, wound healing assays, transwell invasion assays and flow cytometry. The effects of in vivo treatment were evaluated through xenograft experiments. The relationship between miR-182-5p and UBE2T was verified by dual luciferase reporter gene assay. RESULTS: UBE2T was highly expressed in ccRCC cells and tissues. High expression of UBE2T was positively correlated with advanced pathological stage, histological grade, maximum diameter and distant metastasis of the tumor. Multivariate analysis revealed that the UBE2T expression was an independent risk factor for overall survival (OS) and recurrence-free survival (RFS) in patients with ccRCC. Knockdown of UBE2T significantly suppressed proliferation, migration and invasion of RCC. Flow cytometry analysis showed that knocking down UBE2T could promote RCC cell cycle arrest at G2/M phase and increase cell apoptosis. A xenograft model also confirmed that suppression of UBE2T significantly delayed tumor formation and growth in vivo. In addition, miR-182-5p inhibited the expression of UBE2T protein through targeting UBE2T mRNA, and then inhibited the proliferation, migration and invasion of ccRCC. CONCLUSIONS: Our research reveals that miR-182-5p and UBE2T probably play a critical role in ccRCC progression, and they may be the potential therapeutic targets for ccRCC. Source of Funding: The present study was funded by the National Key R&D Program of China (grant no. 2019YFA09006001) and the National Natural Science Foundation of China (grant nos. 81772703 and 81972380) © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e31 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wu Yucai More articles by this author Gong Yanqing More articles by this author Li Xuesong More articles by this author Zhou Liqun More articles by this author Expand All Advertisement PDF DownloadLoading ...

MiR-182-5p inhibits the tumorigenesis of clear cell renal cell carcinoma by repressing UBE2T.

Ubiquitin-conjugating enzyme E2T (UBE2T), a member of the E2 family, has been reported to be overexpressed in certain tumor types and to have an important role in the Fanconi anemia pathway. However, the role of UBE2T in clear cell renal cell carcinoma (ccRCC) has not been clarified. MicroRNAs (miRNAs) participate in tumorigenesis by binding to genes and proteins that regulate cell proliferation or cell apoptosis. The aim of this study was to determine the role of UBE2T and the relationship between miR-182-5p and UBE2T in ccRCC. In the present study, UBE2T expression levels in ccRCC tissues and cells were assessed using real-time quantitative PCR (RT-qPCR) and western blotting. UBE2T protein expression was assessed in a total of 93 ccRCC patients from Peking University First Hospital (PKU) via immunohistochemistry (IHC). The effects of UBE2T knockdown on ccRCC cells were assessed with MTS assays, wound healing assays, Transwell invasion assays and flow cytometry. The effects of in vivo treatment were evaluated through xenograft experiments. The relationship between miR-182-5p and UBE2T was verified with a dual-luciferase reporter gene assay. We found that UBE2T was highly expressed in ccRCC cells and tissues. High UBE2T expression was positively correlated with advanced pathological stage, histological grade, maximum tumor diameter and distant metastasis. Multivariate analysis revealed that UBE2T expression was an independent risk factor for overall survival (OS) and recurrence-free survival (RFS) in patients with ccRCC. Knockdown of UBE2T significantly suppressed RCC cell proliferation, migration and invasion. Flow cytometry analysis showed that UBE2T knockdown promoted RCC cell cycle arrest at G2/M phase and increased cell apoptosis. The xenograft model confirmed that suppression of UBE2T significantly delayed tumor formation and growth in vivo. In addition, miR-182-5p inhibited UBE2T protein expression by targeting UBE2T mRNA and then inhibited the proliferation, migration and invasion of ccRCC cell. Our research reveals that UBE2T likely plays a critical role in ccRCC progression and may be a potential therapeutic target for ccRCC.

MiR-543 impairs breast cancer cell phenotypes by targeting and suppressing ubiquitin-conjugating enzyme E2T (UBE2T)

ABSTRACT Breast cancer, with high morbidity worldwide, is a threat to the life of women. MiR-543 was identified as playing an active part in the development of breast cancer involving multiple molecules. The goal of this study was to explore the molecular mechanisms of the involvement of miR-543 in the development of breast cancer. Quantitative real-time PCR (qRT-PCR) or Western blotting was used to detect mRNA or protein expression. Cell counting kit-8 (CCK-8), and the 5-bromo-2ʹ-deoxyuridine (BrdU), wound healing, and Transwell assays were the main experimental procedures. Furthermore, subcutaneous tumor formation experiments were conducted to detect the function of miR-543 in breast cancer development in vivo. The match of miR-543 and ubiquitin-conjugating enzyme E2T (UBE2T) was detected through a dual-luciferase reporter experiment and RNA pull-down assay. Based on these results, miR-543 exhibited reduced expression in breast cancer tissues and cell lines, whereas UBE2T exhibited high levels. Furthermore, miR-543 directly targeted UBE2T, and a negative correlation between miR-543 and UBE2T was also observed in breast cancer tissues. Moreover, miR-543 overexpression led to inhibition of viability, proliferation, migration, and invasion of breast cancer. Furthermore, miR-543 overexpression undermined the UBE2T promotional effect by inhibiting ERK/MAPK pathway activity in breast cancer cells. Our study revealed that miR-543 impaired breast cancer progression by targeting UBE2T and downregulating UBE2T expression through the ERK/MAPK pathway, which suggested that miR-543 and UBE2T might serve as promising therapeutic gene targets for breast cancer in clinical application.

LncRNA CASC11 Promotes Hepatocellular Carcinoma Progression via Upregulation of UBE2T in a m6A-Dependent Manner.

Hepatocellular carcinoma (HCC) is one of the most frequent malignancies and the third leading cause of cancer-related deaths worldwide. Besides, it has been revealed that long non-coding RNA (LncRNA) cancer susceptibility candidate 11 (CASC11) is involved in cancer progression. However, the functional role and underlying mechanism of CASC11 in HCC remains largely unknown. In this context, here, it was found that CASC11 was upregulated in HCC tissues and associated with tumor grades, metastasis, and prognosis of HCC patients. Functionally, CASC11 facilitated HCC cell proliferation, migration, and invasion in vitro, and enhanced tumor growth and metastasis in vivo. Mechanistically, CASC11 associated with and stabilized Ubiquitin-conjugating enzyme E2T (UBE2T) mRNA. To be specific, it decreased UBE2T N6-methyladenosine (m6A) level via recruiting ALKBH5. Moreover, CASC11 inhibited the association between UBE2T mRNA and m6A reader protein YTHDF2. Taken together, our findings demonstrate the epigenetic mechanism of CASC11 in the regulation of UBE2T expression and possibly provide a novel therapeutic target for HCC treatment.

The expression of circ_0090049 in hepatocellular carcinoma and the molecular regulation mechanism of other biological functions.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in liver cancer. Circular RNA_0090049 (circ_0090049) has been shown to be involved in the advance of HCC. However, the interaction between circ_0090049 and microRNA (miRNA) in HCC has not been studied. Quantitative real-time PCR was used to detect the expression of related genes. Through detection of cell proliferation, migration, invasion, and rate of tumor sphere formation, the capping experiment was carried out to verify the regulatory relationship between miRNA and circ_0090049 or circ_0090049 and ubiquitin-conjugating enzyme E2 T (UBE2T). The expression of related proteins was detected by Western blotting. The interaction of miRNA with circ_0090049 or UBE2T was notarized by Dual-luciferase reporter assay. Xenotransplantation experiments confirmed the function of circ_0090049 in vivo. Circ_0090049 and UBE2T were upregulated in liver cancer. Silencing circ_0090049 reduced the proliferation, migration, invasion, and tumor spheroid formation rate of Huh7 and HCCLM3 cells. MiR-605-5p and miR-548c-3p were identified as targets of circ_0090049, and UBE2T was the target of miR-605-5p and miR-548c-3p. Anti-miR-605-5p, anti-miR-548c-3p or UBE2T overexpression restored the inhibitory effect of circ_0090049 knockdown on HCC cells. Animal experiments confirmed the antitumor effect of silence circ_0090049. Circ_0090049 regulates the expression of UBE2T by regulating miR-605-5p or miR-548c-3p, thereby promoting the development of HCC cells.

Comprehensive analysis of differentially expressed genes reveals the promotive effects of UBE2T on colorectal cancer cell proliferation.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Via analysis using The Cancer Genome Atlas database, the present study identified 1,835 genes that were differentially expressed in CRC, including 811 upregulated and 1,024 downregulated genes. Enrichment analyses using the Database for Annotation, Visualization and Integrated Discovery tool revealed that these differentially expressed genes were associated with the regulation of CRC progression by modulating multiple pathways, such as ‘Cell Cycle, Mitotic’, ‘DNA Replication’, ‘Mitotic M-M/G1 phases’ and ‘ATM pathway’. To identify the key genes in CRC, protein-protein interaction (PPI) network analysis was performed and the hub modules in upregulated and downregulated PPI networks were identified. Ubiquitin-conjugating enzyme E2 T (UBE2T), a member of the E2 family, was identified to be a key regulator in CRC. To the best of our knowledge, the present study was the first to demonstrate that UBE2T expression was upregulated in CRC samples compared with normal tissues. Kaplan-Meier analysis revealed that higher expression levels of UBE2T were associated with worse prognosis compared with lower UBE2T expression levels in CRC. Additionally, the present study demonstrated that knockdown of UBE2T inhibited CRC cell proliferation. Flow cytometry assays revealed that UBE2T knockdown induced cell cycle arrest at G1 phase and apoptosis in vitro. These results suggested that UBE2T may be a novel potential biomarker for CRC.

Upregulation of ubiquitin-conjugating enzyme E2T (UBE2T) predicts poor prognosis and promotes hepatocellular carcinoma progression

ABSTRACT Reportedly, ubiquitin-conjugating enzyme E2T (UBE2T) is closely related to the progression of several malignancies. This work is aimed to probe the role of UBE2T in the progression of hepatocellular carcinoma (HCC) patients. The microarray analysis was executed to screen the differentially expressed genes (DEGs) in HCC tissues. The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA2) databases, PCR and immunohistochemistry were utilized to validate the dysregulation of UBE2T in HCC. Kaplan-Meier analysis was employed to determine the relationship between UBE2T expression and the prognosis of HCC patients. PCR was carried out to detect UBE2T protein expression in HCC cell lines. Cell Counting Kit-8 (CCK-8) assay and 5-bromo-2ʹ-deoxyuridine (BrdU) experiments were conducted to examine the proliferation of HCC cells. Scratch healing and Transwell experiments were conducted to examine the migration of HCC cells. Bioinformatics analysis and dual-luciferase reporter gene experiments predicted and validated the targeting relationship with miR-212-5p and UBE2T. We found that UBE2T expression was remarkably up-modulated in HCC tissues and cell lines, and its high expression was linked to a worse prognosis in HCC patients. UBE2T overexpression enhanced HCC cell proliferation and migration. Additionally, UBE2T was verified as a downstream target of miR-212-5p. In conclusion, UBE2T overexpression is markedly linked to unfavorable prognosis in HCC patients. UBE2T, regulated by miR-212-5p, significantly enhances the malignant phenotypes of HCC cells, which can be used as a target for HCC diagnosis and prognosis.

Expression of ubiquitin-conjugating enzyme E2T in colorectal cancers and clinical implications.

Ubiquitin-conjugating enzyme E2T (UBE2T) plays a significant role in carcinogenesis. Previous studies have demonstrated that UBE2T promotes the development and progression of numerous types of cancer. However, the association between UBE2T expression and colorectal cancer (CRC) remains unclear. In the present study, UBE2T protein expression was examined in the tissues of patients with CRC via immunohistochemistry. In addition, UBE2T expression data and corresponding clinical information were obtained from The Cancer Genome Atlas (TCGA). In the clinical samples, the associations between UBE2T expression and clinicopathological factors were evaluated by the χ2 or Fisher's exact tests. In TCGA data, associations between UBE2T expression and clinical characteristics were evaluated using a logistic regression model. Overall survival was analyzed using Kaplan-Meier and Cox regression analyses. Reverse transcription-quantitative PCR (RT-qPCR) and western blotting assays were used to examine UBE2T expression in normal and CRC cell lines. Gene set enrichment analysis (GSEA) was performed on the dataset from TCGA. UBE2T protein was highly expressed in the cytoplasm of tumor cells in 29/50 clinical samples, whereas in the adjacent normal tissues, it was only highly expressed in 2/50 samples. Furthermore, UBE2T expression was associated with the N classification (P<0.001), clinical TNM stage (P<0.001) and histological grade of tumors (P=0.010). Survival analysis showed an association between high UBE2T expression and poor survival rate in patients with CRC (P=0.002). Cox regression analysis also revealed that UBE2T expression was an independent prognostic factor for these patients (P=0.006). RT-qPCR and western blotting showed that UBE2T was expressed in CRC cell lines at higher levels than that in a normal colon cell line. Analysis of TCGA data revealed that UBE2T was highly expressed in tumor samples compared with normal samples, but was not associated with prognosis. GSEA showed that high expression of UBE2T was associated with the Kyoto Encyclopedia of Genes and Genomes pathways ‘cell cycle’, ‘oxidative phosphorylation’, ‘DNA replication’, ‘p53 signaling pathway’, ‘ubiquitin mediated proteolysis’ and ‘pentose phosphate pathway’. These results indicate that UBE2T may play an important role in the progression of CRC and serve as a potential prognostic factor during the treatment of cancer.

Ubiquitin-conjugating enzyme E2T regulates cell proliferation and migration in cholangiocarcinoma.

Ubiquitin-conjugating enzyme E2T (UBE2T) is overexpressed in several human cancer cells, but a role in cholangiocarcinoma (CAA) progression has not been investigated. We analyzed the expression of UBE2T in CAA tissues. Then, we generated UBE2T deregulation models in which it was overexpressed or silenced, and examined the effects on CAA malignant progression by flow cytometry, western blot, MTT assay, wound healing assay and transwell assay. We report the involvement of UBE2T in CAA malignant progression. UBE2T was found to be highly expressed in human CAA cells both in vitro and in vivo. Overexpression of UBE2T significantly enhanced epithelial-to-mesenchymal transition, proliferation, migration and invasion of CAA cells in vitro, while silencing UBE2T had opposing effects. Furthermore, UBE2T appears to exert its effects via the mammalian target of rapamycin (mTOR) pathway as the cellular effects caused by UBE2T overexpression are inhibited by the mTOR inhibitor rapamycin. Our findings suggest that UBE2T may have potential as a new therapeutic target for the prevention or treatment of CAA.

Ubiquitin-conjugating enzyme E2T(UBE2T) promotes colorectal cancer progression by facilitating ubiquitination and degradation of p53

The expression level of Ubiquitin-conjugating enzyme E2T (UBE2T) is upregulated in various types of human tumors. We explored the correlation and regulatory mechanism of UBE2T in the development of colorectal cancer (CRC). Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to examine the expression of UBE2T in the CRC tissues and cell lines. Immunohistochemical staining, spearman correlation analysis, and Kaplan Meier-survival analysis were used to demonstrate the correlation between UBE2T high expression level and the clinical characteristics of malignant patients and the overall survival. The proliferation, apoptosis, migration and invasion of CRC cells were analyzed by cell transfection, MTT, colony formation, scratch assay, transwell, and flow cytometry. Furthermore, the expression of cell proliferation and apoptosis related proteins and ubiquitination of p53 were detected by western blot. UBE2T was up-regulated in CRC tissues and cell lines, and high expression level of UBE2T was correlated with the clinical characteristics of malignant of CRC patients (P<0.05), and patients with high expression level of UBE2T had lower overall survival (P=0.0455). In addition, UBE2T could promote the growth, proliferation, invasion and metastasis of CRC cells and inhibit the apoptosis. At the same time, knockdown of UBE2T inhibited the growth of transplanted tumor in mice of subcutaneous CRC model. Moreover, our experimental results proved that UBE2T regulated the expression of downstream related proteins through ubiquitination of p53 protein to promote the occurrence and development of CRC. Our study elucidated that high expression of UBE2T would enhance the development of CRC, and then further explored its molecular mechanism both in vitro and in vivo. The results indicated that UBE2T facilitated ubiquitination and degradation of p53, which predicts the possibility of UBE2T as one of molecular diagnosis markers, prognostic indicators and therapeutic drug targets of CRC patients.

Identification of UBE2T as an independent prognostic biomarker for gallbladder cancer.

Gallbladder cancer is the most common biliary tract malignant tumor, with unfavorable patient outcomes. The present study aimed to identify potential diagnostic or prognostic biomarkers for gallbladder cancer. To do so, differentially expressed genes in the gallbladder walls and tumor tissues of patients with gallbladder cancer were analyzed via microarray. Furthermore, a protein-protein interaction network was constructed and genes with a degree score >10 were selected as hub genes. As ubiquitin conjugating enzyme E2T (UBE2T) was considered to be a hub gene, its expression was assessed via reverse transcription-quantitative (RT-q)PCR and immunohistochemistry (IHC). In addition, the association between UBE2T expression and the clinicopathological characteristics of patients with gallbladder cancer was analyzed using the χ2 test. Furthermore, all patients were divided into high- and low groups based on UBE2T expression level and overall survival analysis was performed. Univariate and multivariate Cox regression analyses were performed to determine whether UBE2T may serve as an independent risk factor for gallbladder cancer. The results demonstrated that UBE2T expression was upregulated in the gallbladder walls and tumor tissues of patients with gallbladder cancer. Furthermore, UBE2T expression level was confirmed to be upregulated following RT-qPCR, and results from IHC demonstrated that UBE2T was predominantly expressed in the cytoplasm of gallbladder cancer cells. In addition, high UBE2T expression level was associated with clinical stage, T classification, N classification and M classification. The results from Univariate and multivariate analyses indicated that UBE2T expression level may be considered as an independent risk factor for gallbladder cancer. Taken together, the findings from this study suggested that high UBE2T expression level may contribute to the poor prognosis of patients with gallbladder cancer, and that UBE2T may act as an independent prognostic biomarker for these patients.

UBE2T promotes glioblastoma invasion and migration via stabilizing GRP78 and regulating EMT.

Glioblastoma (GBM) generally has a dismal prognosis, and it is associated with a poor quality of life as the disease progresses. However, the development of effective therapies for GBM has been deficient. Ubiquitin-conjugating enzyme E2T (UBE2T) is a member of the E2 family in the ubiquitin-proteasome pathway and a vital regulator of tumour progression, but its role in GBM is unclear. In this study, we aimed to clarify the role of UBE2T in GBM. Bioinformatics analysis identified UBE2T as an independent risk factor for gliomas. Immunohistochemistry was used to measure UBE2T expression in GBM and normal tissue samples obtained from patients with GBM. The effects of UBE2T on GBM cell invasion and migration were analysed using the Transwell assay. BALB/c nude mice were used for the in vivo assays. Immunoblotting and immunoprecipitation were performed to determine the molecular mechanisms. UBE2T was highly expressed in GBM tissues, and its expression was linked to a poor prognosis. In vitro, depletion of UBE2T significantly suppressed cell invasion and migration. Moreover, UBE2T depletion suppressed the growth of GBM subcutaneous tumours in vivo. Further experiments revealed that UBE2T suppressed invasion and migration by regulating epithelial- mesenchymal transition (EMT) via stabilising GRP78 in GBM cells. We uncovered a novel UBE2T/GRP78/EMT regulatory axis that modulates the malignant progression and recurrence of GBM, indicating that the axis might be a valuable therapeutic target.

Role of ubiquitin-conjugating enzyme E2T in the carcinogenesis and progression of pancreatic cancer.

Ubiquitin-conjugating enzyme E2T (UBE2T) is a recently discovered oncogenic protein. Numerous studies reported that UBE2T is highly expressed in various types of human cancer; however, its role in the carcinogenesis and progression of pancreatic cancer remains unknown. The aim of the present study was to investigate the role of UBE2T in pancreatic cancer progression through in vitro experiments in pancreatic cancer tissues and cell lines. The results obtained in the present study demonstrated that UBE2T served an important role in the initiation and progression of pancreatic cancer. Furthermore, increased expression of UBE2T in human pancreatic cancer tissues and pancreatic cancer cells was observed compared with normal tissues and cells. The effect of upregulating and downregulating UBE2T in pancreatic cancer cell lines was investigated using the MTT, wound-healing and migration and invasion assays. The results demonstrated that overexpression of UBE2T significantly promoted pancreatic cancer cell proliferation, migration and invasion compared with controls. However, UBE2T downregulation resulted in the inhibition of pancreatic cancer cell proliferation, migration and invasion. In addition, the results demonstrated that UBE2T may promote the epithelial mesenchymal transition in pancreatic cancer cells.

Expression of ubiquitin-conjugating enzyme E2T in gastric cancer and para-carcinoma tissues

Expression of ubiquitin-conjugating enzyme E2T in gastric cancer and para-carcinoma tissues

High ubiquitin conjugating enzyme E2 T mRNA expression and its prognostic significance in lung adenocarcinoma

Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer with a high mortality disease which has been positioned the first and second cancer morbidity of men and women in China, separately. Our study was to assess the prognostic meaningful of ubiquitin conjugating enzyme E2 T (UBE2T) expression in LUAD dependent on data acquired from The Cancer Genome Atlas (TCGA) and so as to increase further knowledge into the biological pathways involved in LUAD pathogenesis related to UBE2T.Information on gene expression and comparing clinical data were recognized and downloaded from TCGA. Gene set enrichment analysis (GSEA) created an arranged list of all genes s indicated by their connection with UBE2T expression.Our study cohort included 265 (54.5%) female and 221 (36.0%) male patients. The scatter plot and paired plot showed the difference of UBE2T expression between normal and tumor samples (P < .01). Overall survival (OS) analysis demonstrated that LUAD with UBE2T-high had a more terrible prognosis than that with UBE2T-low (P < .01). Multivariate analysis with the cox proportional hazards model indicated that the expression of UBE2T (hazard ratio [HR]: 1.28; 95% Confidence Interval (CI): 1.06–1.56; P = .011) and stage (HR: 2.02; 95% CI: 1.27–3.21; P = .003) were independent prognostic factors for patients with LUAD. The GSEA results showed that cell cycle, DNA replication, RNA degradation, oxidative phosphorylation, pathogenic Escherichia coli infection, citrate cycle tricarboxylic acid cycle, Alzheimer's disease, P53 signaling pathway, and purine metabolism are differentially enriched in UBE2T high expression phenotype.Our study found that the expression of UBE2T was significantly increased in LUAD patients and associated with several clinical features. UBE2T may be a potentially useful prognostic molecular biomarker of bad survival in LUAD, while further experimental ought to be performed to demonstrate the biologic effect of UBE2T.

Ubiquitin-conjugating enzyme E2T knockdown suppresses hepatocellular tumorigenesis via inducing cell cycle arrest and apoptosis.

BACKGROUNDHepatocellular carcinoma (HCC) is now the most common primary liver malignancy worldwide, and multiple risk factors attribute to the occurrence and development of HCC. Recently, increasing studies suggest that ubiquitin-conjugating enzyme E2T (UBE2T) serves as a promising prognostic factor in human cancers, although the molecular mechanism of UBE2T in HCC remains unclear.AIMTo investigate the clinical relevance and role of UBE2T in HCC development.METHODSUBE2T expression in HCC tissues from the TCGA database and its association with patient survival were analyzed. A lentivirus-mediated strategy was used to knock down UBE2T in HCC cells. qRT-PCR and Western blot assays were performed to check the effect of UBE2T silencing in HCC cells. Cell growth in vitro and in vivo was analyzed by multiparametric high-content screening and the xenograft tumorigenicity assay, respectively. Cell cycle distribution and apoptosis were determined by flow cytometry. The genes regulated by UBE2T were profiled by microarray assay.RESULTSUBE2T was overexpressed in HCC tissues compared with paired and non-paired normal tissues. High expression of UBE2T predicted a poor overall survival in HCC patients. In vitro, lentivirus-mediated UBE2T knockdown significantly reduced the viability of both SMMC-7721 and BEL-7404 cells. In vivo, the xenograft tumorigenesis of SMMC-7721 cells was largely attenuated by UBE2T silencing. The cell cycle was arrested at G1/S phase in SMMC-7721 and BEL-7404 cells with UBE2T knockdown. Furthermore, apoptosis was increased by UBE2T knockdown. At the molecular level, numerous genes were dysregulated after UBE2T silencing, including IL-1B, FOSL1, PTGS2, and BMP6.CONCLUSIONUBE2T plays an important role in cell cycle progression, apoptosis, and HCC development.

UBE2T promotes proliferation via G2/M checkpoint in hepatocellular carcinoma.

BackgroundGrowing evidence suggests that the ubiquitin-proteasome system is involved in the pathogenesis and recurrence of hepatocellular carcinoma (HCC); yet, little is known about the role of ubiquitin-conjugating enzyme E2T (UBE2T) in HCC.Materials and methodsUBE2T levels were detected in HCC tissues and hepatoma cell lines using quantitative reserve transcriptase-polymerase chain reaction and Western blot analysis. Next, the changes of phenotypes after UBE2T knockdown or overexpression were evaluated using in vitro methods. Finally, the mechanism of UBE2T in HCC was tested using ex vivo and in vivo methods.ResultsIn the present study, we reported that UBE2T mRNA and protein levels were significantly upregulated in HCC tissues compared to adjacent non-tumor tissues. Additionally, suppression of UBE2T expression inhibited proliferation, colony formation, tumorigenesis, migration, and invasion of hepatoma cells, whereas UBE2T overexpression led to the opposite outcomes. Moreover, suppression of UBE2T expression resulted in an increase in G2/M phase and a decrease in the percentage of cells in G1 phase, which indicated a cell cycle arrest at the G2/M phase. In contrast, the percentage of cells in G2/M phase decreased following UBE2T overexpression. Further study indicated that UBE2T regulated the G2/M transition by modulating cyclin B1 and cyclin-dependent kinase 1.ConclusionTaken together, the findings of the present study uncover biological functions of UBE2T in hepatoma cells, and delineate preliminary molecular mechanisms of UBE2T in modulating HCC development and progression.

UBE2T promotes proliferation and regulates PI3K/Akt signaling in renal cell carcinoma.

Renal cell carcinoma (RCC) is a common malignant tumor globally. The overall survival of patients with RCC is poor; one important factor is tumor heterogeneity. Ubiquitin-conjugating enzyme E2T (UBE2T) has been reported to act as an oncogene in various types of cancer; however, its role in RCC has yet to be investigated. In the present study, UBE2T was demonstrated via reverse transcription-quantitative PCR analysis to be significantly upregulated in RCC samples and cell lines compared with in normal tissue and cells. Additionally, UBE2T expression was significantly associated with late tumor stage and high grade in patients with RCC, and patients with high UBE2T expression exhibited poor prognosis compared with patients with low expression. Following knockdown of UBE2T in 786-O cells using RNA interference technology, the proliferation and colony formation of cells were inhibited as determined by an MTT assay and crystal violet staining, respectively; however, the migration and invasion of 786-O cells were not affected, as determined by wound-healing assay and Transwell assays, respectively. Xenograft RCC tumor growth in vivo was also significantly suppressed. The expression levels of two mesenchymal cell markers, N-cadherin and vimentin, were reduced following UBE2T knockdown, whereas E-cadherin and fibronectin levels were increased as determined by western blotting, indicating that epithelial-mesenchymal transition was suppressed. In addition, the phosphorylation levels of PI3K, Akt and mTOR were notably decreased following UBE2T knockdown, but were increased when UBE2T was overexpressed. Wortmannin, an Akt inhibitor, reversed the UBE2T overexpression-induced increase in the phosphorylation of PI3K, Akt and mTOR. Similarly, the UBE2T overexpression-induced promotion of 786-O cell proliferation was also attenuated by wortmannin. In conclusion, UBE2T promoted the proliferation of RCC cells by regulating PI3K/Akt signaling, suggesting it may be a novel target for the treatment of patients with RCC.