UBE2T promotes hepatocellular carcinoma cell growth via ubiquitination of p53

Liu, Liping; Yang, Mei; Peng, Quanzhou; Li, Mingyue; Zhang, Yusen; Guo, Yuehua; Yang, Chong‐Ren; Bao, Shaowen

doi:10.1016/j.bbrc.2017.09.091

Cited by 79 publications

(90 citation statements)

References 23 publications

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“…The roles of autophagy in OC have been widely explored [27,28]. Considering the regulatory effects of UBE2T on AKT [18] and p53 [12], which are vital regulators of autophagy [28], we explored the function of UBE2T in autophagy of OC cells. As the results shown, UBE2T knockdown activated the autophagy of OC cells indicating by upregulated BECN1, accumulated LC3B, and decreased p62 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Upregulation of UBE2T, severing as an unfavorable prognostic indicator, has been con rmed in both solid tumors, such as gastric cancer [9,10], hepatocellular carcinoma [11,12], breast cancer [13], lung cancer [13,14], nasopharyngeal carcinoma [15], osteosarcoma [16], prostate cancer [17] and renal cell carcinoma [18], and non-solid tumor like multiple myeloma (MM) [19]. Consistently, UBE2T depletion notably suppresses malignant progression via modulation the activity AKT [18] and p53 [12]. Nevertheless, the expression, clinical signi cance, functions and the corresponding mechanism of UBE2T has not been revealed in OC.…”

Section: Introductionmentioning

confidence: 99%

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UBE2T is upregulated, predicts poor prognosis, and promotes cell proliferation and invasion via inhibiting autophagy in ovarian cancer

Huang

Xiao

et al. 2020

Preprint

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Background: Aberrant upregulation and oncogenic roles of UBE2T have been revealed in several cancers. However, the expression, clinical significance, and functions of UBE2T has not been explored in ovarian cancer (OC).Methods: In this study, the mRNA and protein expression of UBE2T in OC were detected via analyzing the online databases and immunohistochemical staining. Moreover, relations of UBE2T expression with clincopathological features and prognosis OC patients were further analyzed. Besides, the effects of UBE2T knockdown on growth, proliferation, and invasion of OC cells were investigated by CCK-8, plate clone formation, and Transwell assays. Finally, the underlying mechanism of UBE2T associated functions in OC was analyzed.Results: The results indicated that UBE2T was significantly upregulated in OC tissues. UBE2T expression was notably correlated with clinical features such as primary T stage, TNM stage in OC patients. UBE2T, acting as an independent prognostic indicator, was inversely associated with prognosis of OC patients. UBE2T knockdown remarkably suppressed the growth, proliferation, and invasion of OC cells indicating by impaired cell viability, less cell clones and invasive cells. Mechanistically, the oncogenic roles of UBE2T was exerted by inhibiting autophagy via maintaining AKT/mTOR activity in OC.Conclusion: Collectively, our findings confirm UBE2T upregulation predicts poor prognosis and promotes malignant progression via suppressing autophagy in OC, suggesting the promising values of UBE2T both in diagnosis and treatment of OC.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

UBE2T is upregulated, predicts poor prognosis, and promotes cell proliferation and invasion via inhibiting autophagy in ovarian cancer

Huang

Xiao

et al. 2020

Preprint

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“…It combines with a speci c ubiquitin E3 ligase to degrade speci c substrates, contributing to DNA repair in the Fanconi anemia pathway and playing a key role in cell proliferation and the maintenance of genomic stability [50]. Recently, UBE2T expression has been reported to be signi cantly upregulated in hepatocellular carcinoma [10], renal cell carcinoma [51], prostate cancer [15], breast cancer, and lung adenocarcinoma [52], and its high expression is associated with poor prognosis in patients. Consistently, after integrating the data on gene expression and prognostic value obtained from different databases, we found that UBE2T was signi cantly overexpressed in OC compared to normal ovarian tissues, and that its high expression was associated with poor prognosis in both OC and serous ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Multiple evidence indicates that UBE2T acts as an oncogene in a variety of tumors, but its molecular mechanism of action varies in different types of cancer. One study showed that UBE2T plays a role in the proliferation and invasion of hepatocellular carcinoma cells by regulating the G2/M transition of the cell cycle through the cyclin B1-CDK1 pathway [55], while another study found that UBE2T enhances p53 ubiquitination and degradation, promoting the carcinogenesis of hepatocellular carcinoma [10]. Furthermore, UBE2T downregulation reduces the activity of the PI3K/Akt signaling pathway, thus inhibiting the proliferation and migration of renal cell carcinoma [51] and osteosarcoma cells [56].…”

Section: Discussionmentioning

confidence: 99%

“…UBE2T, a member of the UBE2 family, was the rst to be de ned as a key factor in the Fanconi anemia pathway [9]. Several studies have con rmed that UBE2T plays a carcinogenic role in various types of cancer, including hepatocellular carcinoma, as well as lung, breast, stomach, bladder, and prostate cancer, but its expression level and prognostic value in OC are still unclear [10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

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Increased expression of UBE2T predicting poor survival of ovarian cancer: based on comprehensive analysis of UBE2s, clinical samples and the GEO database

Zou

et al. 2020

Preprint

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Background： Ubiquitin-conjugating enzymes E2 (UBE2) have been reported in the microenvironment of various malignant tumors, but their correlation with ovarian cancer remains elusive.Methods: The Oncomine, GEPIA, Kaplan-Meier Plotter, cBioPortal, and STRING databases were used to systematically analyze the expression pattern, prognostic value, genetic variation, and biological function of 12 members of the UBE2 gene family in ovarian cancer. UBE2T exhibited the greatest correlation with ovarian cancer and was thus further examined. Gene set enrichment analysis (GSEA), as well as analyses of function and pathway enrichment, somatic mutations, copy number variation, and methylation were performed, and the correlation with immune cell infiltration was examined to explore the mechanism underlying aberrant UBE2T expression. Finally, the expression and prognostic value of UBE2T in ovarian cancer were verified by immunohistochemical evaluation of 131 clinical ovarian samples and the Gene Expression Omnibus (GEO) database (GSE51088, GSE73614, and GSE63885 datasets) analysis.Results: The mRNA levels of UBE2C , UBE2N , UBE2S , and UBE2T were significantly upregulated in ovarian cancer compared with those in normal ovarian tissue. In patients with ovarian serous carcinoma, UBE2A , UBE2B , UBE2C , UBE2G , and UBE2T upregulation and UBE2R2 downregulation were associated with poor overall survival. Moreover, UBE2A , UBE2N , and UBE2T upregulation and UBE2G and UBE2R2 downregulation were associated with poor progression-free survival. Immunohistochemistry revealed that UBE2T was significantly upregulated in ovarian malignant tumors compared with that in borderline tumors, benign tumors, and normal ovarian tissues, and its high expression was associated with poor prognosis. The Cox model showed that UBE2T upregulation was an independent risk factor affecting the prognosis of ovarian cancer (hazard ratio: 4.095, P= 0.029). The above results were verified in the GEO database. In addition, UBE2T was associated with specific immune cells and mainly involved in cell cycle-related events. Genomic analysis showed that TP53 and TTN mutations were associated with UBE2T expression. Gene copy number amplification and hypomethylation may be responsible for UBE2T upregulation in ovarian cancer.Conclusions: UBE2 family members may play a role in the development of ovarian cancer. Specifically, UBE2T could serve as a new prognostic marker and therapeutic target for this disease.

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UBE2T promotes β‐catenin nuclear translocation in hepatocellular carcinoma through MAPK/ERK‐dependent activation

et al. 2022

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Ubiquitin-conjugating enzyme E2T (UBE2T) has been implicated in many types of cancer including hepatocellular carcinoma (HCC). Epithelial-mesenchymal transition (EMT) process plays a fundamental role during tumor metastasis and progression. However, the molecular mechanisms underlying EMT in HCC in accordance with UBE2T still remain unknown. In this study, we showed that UBE2T overexpression augmented the oncogenic properties and specifically EMT in HCC cell lines, while its silencing attenuated them. UBE2T affected the activation of EMT-associated signaling pathways: MAPK/ERK, AKT/mTOR, and Wnt/b-catenin. In addition, we revealed that the epithelial protein complex of E-cadherin/b-catenin, a vital regulator of signal transduction in tumor initiation and progression, was totally disrupted at the cell membrane. In particular, we observed that UBE2T overexpression led to E-cadherin loss accompanied by a simultaneous elevation of both cytoplasmic and nuclear b-catenin, while its silencing resulted in a strong E-cadherin turnover at the cell membrane. Interestingly, chemical inhibition of the MAPK/ERK, AKT/mTOR, and Wnt/bcatenin signaling pathways demonstrated that the nuclear translocation of b-catenin and subsequent EMT was enhanced mainly by MAPK/ERK. Collectively, our findings demonstrate the UBE2T/MAPK-ERK/b-catenin axis as a critical regulator of cell state transition and EMT in HCC.

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UBE2T promotes hepatocellular carcinoma cell growth via ubiquitination of p53

Cited by 79 publications

References 23 publications

UBE2T is upregulated, predicts poor prognosis, and promotes cell proliferation and invasion via inhibiting autophagy in ovarian cancer

UBE2T is upregulated, predicts poor prognosis, and promotes cell proliferation and invasion via inhibiting autophagy in ovarian cancer

Increased expression of UBE2T predicting poor survival of ovarian cancer: based on comprehensive analysis of UBE2s, clinical samples and the GEO database

UBE2T promotes β‐catenin nuclear translocation in hepatocellular carcinoma through MAPK/ERK‐dependent activation

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