Identification of overexpressed genes in hepatocellular carcinoma, with special reference to <i>ubiquitin‐conjugating enzyme E2C</i> gene expression

Ieta, Keisuke; Ojima, Eiki; Tanaka, Fumiaki; Nakamura, Yoshito; Haraguchi, Naotsugu; Mimori, Koshi; Inoue, Hiroshi; Kuwano, Hiroyuki; Mori, Masaki

doi:10.1002/ijc.22605

Cited by 96 publications

(77 citation statements)

References 32 publications

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“…Another example of a gene persistently altered by the MF diet that might contribute to the development of liver dysfunction is Ubiquitin‐conjugating enzyme 2c ( Ube2c ). Ube2c has been identified as a hepatocellular carcinoma gene 81, 82 and we observed elevated expression of Ube2c already at the age of 6 months in the MF‐exposed mice (Supporting Information Fig. 3B) but the INT diet appears to reverse this effect at young age.…”

Section: Discussionmentioning

confidence: 71%

Intermittent calorie restriction largely counteracts the adverse health effects of a moderate‐fat diet in aging C57BL/6J mice

Lute

Boekschoten

Dijk

et al. 2017

Molecular Nutrition Food Res

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ScopeCalorie restriction (CR) has been shown to extend life‐ and health‐span in model species. For most humans, a life‐long CR diet is too arduous to adhere to. The aim of this study was to explore whether weekly intermittent CR can (1) provide long‐term beneficial effects and (2) counteract diet‐induced obesity in male aging mice.Methods and resultsIn this study, we have exposed C57Bl/6J mice for 24 months to an intermittent (INT) diet, alternating weekly between CR of a control diet and ad libitum moderate‐fat (MF) feeding. This weekly intermittent CR significantly counteracted the adverse effects of the MF diet on mortality, body weight, and liver health markers in 24‐month‐old male mice. Hepatic gene expression profiles of INT‐exposed animals appeared much more comparable to CR‐ than to MF‐exposed mice. At 12 months of age, a subgroup of MF‐exposed mice was transferred to the INT diet. Gene expression profiles in the liver of the 24‐month‐old diet switch mice were highly similar to the INT‐exposed mice. However, a small subset of genes was consistently changed by the MF diet during the first phase of life.ConclusionWeekly intermittent CR largely, but not completely, reversed adverse effects caused by a MF diet.

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Section: Discussionmentioning

confidence: 71%

Intermittent calorie restriction largely counteracts the adverse health effects of a moderate‐fat diet in aging C57BL/6J mice

Lute

Boekschoten

Dijk

et al. 2017

Molecular Nutrition Food Res

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“…Our study demonstrated that siRNA-mediated suppression of UBE2C expression inhibited the growth rate of CRC cells with accumulation of cyclins A and B1, which was consistent with earlier reports. 13,16 Interestingly, we found that down-regulation of UBE2C expression caused inhibition of cell viability by arresting cells in the G2/M phase followed by induction of apoptosis in CRC cells. UBE2C expression in CRC cell lines was found to be inversely associated with cyclin A and B1 in concordance with the mechanistic model of UBE2C function.…”

Section: Discussionmentioning

confidence: 86%

“…3,6 Overexpression of UBE2C at the mRNA level has been reported in a number of cancer cell lines and primary tumors, whereas only low levels were found in normal tissues. 7 The oncogenic role of UBE2C is also reported in thyroid, 8 ovarian, 9 esopha-geal, 10 breast, 11 lung, 12 liver, 13 and brain 14 tumors. Takahashi et al 15 suggest that overexpression of UBE2C may play an important role in advanced colon cancer with liver metastases and that this overexpression may be a result of chromosomal amplification at the UBE2C locus, 20q13.1.…”

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confidence: 98%

Bortezomib Stabilizes Mitotic Cyclins and Prevents Cell Cycle Progression via Inhibition of UBE2C in Colorectal Carcinoma

Bavi

Uddin

Ahmed

et al. 2011

The American Journal of Pathology

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Substantial evidence implicates the ubiquitin-conjugating enzyme E2C (UBE2C) gene, in several human cancers, including colorectal carcinoma (CRC). We therefore investigated the prognostic value of UBE2C alterations in CRC and UBE2C signaling in CRC cell lines. UBE2C protein expression and UBE2C gene copy number were evaluated on clinical samples by immunohistochemistry and fluorescence in situ hybridization in a TMA format. The effect of the proteasome inhibitor bortezomib and small-interfering RNA knockdown was assessed by apoptotic assays and immunoblotting. UBE2C dysregulation was associated with proliferative marker Ki-67, accumulation of cyclin A and B1, and a poor overall survival. UBE2C expression was an independent prognostic marker in early-stage (I and II) CRC. UBE2C depletion resulted in suppression of cellular growth and accumulation of cyclin A and B1. In vitro, bortezomib treatment of CRC cells caused inhibition of cell viability via down-regulation of UBE2C. UBE2C knockdown by bortezomib or transfection with specific small-interfering RNA against UBE2C also caused cells to be arrested at the G2/M level, leading to accumulation of cyclin A and cyclin B1. In vivo, a significant reduction in tumor volume and weight was noted in mice treated with a combination of subtoxic doses of oxaliplatin and bortezomib compared with treatment with oxaliplatin or bortezomib alone. Altogether, our results suggest that UBE2C and the ubiq- Although colorectal cancer (CRC) is a major cause of mortality and morbidity worldwide, various therapeutic modalities followed in clinical practice are not life saving. More recently, advances in understanding of tumor biology have led to the development of targeted therapies, 1 allowing progress in the treatment of CRC. 2 The ubiquitin proteasome system is important for the orchestration of several important cell cycle events, such as proteolysis of cyclin-dependent kinase and their inhibitors. 3,4 Proper cell cycle progression is orchestrated by the controlled oscillation of a series of cell cycle events. Deregulation of appropriate cell cycle control often results in chromosomal instability, which is a potential trigger for the initiation of cancer. 5 In this system, substrate molecules are regulated for degradation by ubiquitinactivating enzyme (E1), ubiquitin-conjugating enzyme (E2), and E3 ligase. The ubiquitin-conjugating enzyme E2C (UBE2C), also known as UBCH10, along with the E3 ligase of the anaphase-promoting complex catalyze the ubiquitination of mitotic cyclins A and B1, as well as securin. 3,6 UBE2C is essential for cell cycle progression, and mutation of its active site cysteine confers a dominant-negative phenotype. 3,6 Overexpression of UBE2C at the mRNA level has been reported in a number of cancer cell lines and primary tumors, whereas only low levels were found in normal tissues. 7 The oncogenic role of UBE2C is also reported in thyroid, 8 ovarian, 9 esopha-

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“…Ubiquitin-conjugating enzyme E2C (UBE2C) belongs to the E2 family, and is involved in mitotic cyclin destruction and cell cycle progression (8). UBE2C has been implicated in the carcinogenesis of certain tumors (9,10), and is overexpressed in various human cancers, including breast, esophageal, colon, lung, liver and ovarian cancers (11)(12)(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

High expression of UBE2C is associated with the aggressive progression and poor outcome of malignant glioma

Kang

Zhang

et al. 2016

Oncology Letters

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Abstract. Ubiquitin-conjugating enzyme E2C (UBE2C) is a key regulator of cell cycle progression and is involved in the tumorigenesis of a variety of cancers. Previous studies have demonstrated that UBE2C is an important factor in the malignant progression of astrocytic tumors. However, the association between UBE2C expression and clinical prognosis of glioma patients has not been defined. In the present study, the expression of UBE2C in gliomas and non-cancerous brain tissues were detected by microarray and immunohistochemical analysis. The association between UBE2C expression and clinicopathological characteristics of the glioma patients was evaluated. The Kaplan-Meier method and multivariate Cox's proportional hazards model were used to analyze the survival time of the patients. The results demonstrated that the expression levels of UBE2C in anaplastic gliomas and glioblastoma (GBM) patients were significantly higher compared to low-grade gliomas, in microarray and immunohistochemistry analysis. A higher UBE2C expression was associated with a significantly decreased overall survival time in patients possessing anaplastic gliomas (P<0.01) and GBMs (P<0.05). Multivariate analysis of 80 GBM patients revealed that UBE2C expression was an independent prognostic factor. To the best of our knowledge, the present data suggest for the first time that UBE2C overexpression is strongly associated with an aggressive progression and poor outcome of malignant glioma. Therefore, UBE2C overexpression may be used as a predictor of poor prognosis in patients with malignant glioma.

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Identification of overexpressed genes in hepatocellular carcinoma, with special reference to ubiquitin‐conjugating enzyme E2C gene expression

Cited by 96 publications

References 32 publications

Intermittent calorie restriction largely counteracts the adverse health effects of a moderate‐fat diet in aging C57BL/6J mice

Intermittent calorie restriction largely counteracts the adverse health effects of a moderate‐fat diet in aging C57BL/6J mice

Bortezomib Stabilizes Mitotic Cyclins and Prevents Cell Cycle Progression via Inhibition of UBE2C in Colorectal Carcinoma

High expression of UBE2C is associated with the aggressive progression and poor outcome of malignant glioma

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