Dominant negative Ubiquitin-conjugating enzyme E2C sensitizes cervical cancer cells to radiation

Bose, Mayil Vahanan; Gopisetty, Gopal; Ganesarajah, Selvaluxmy; Rajkumar, Thangarajan

doi:10.3109/09553002.2012.702299

Cited by 16 publications

(18 citation statements)

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“…Abundant experimental evidence has shown a role for Ube2c in human tumor initiation and progression. On the other hand, there are very few reports that implicate Ube2c in DNA damage response to radiation [49, 50]. Moreover, the mechanistic details of Ube2c response to radiation, as well as their pathophysiological significance remain unexplored.…”

Section: Discussionmentioning

confidence: 99%

Comparison of gene expression response to neutron and x-ray irradiation using mouse blood

Broustas

Harken

et al. 2017

BMC Genomics

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BackgroundIn the event of an improvised nuclear device detonation, the prompt radiation exposure would consist of photons plus a neutron component that would contribute to the total dose. As neutrons cause more complex and difficult to repair damage to cells that would result in a more severe health burden to affected individuals, it is paramount to be able to estimate the contribution of neutrons to an estimated dose, to provide information for those making treatment decisions.ResultsMice exposed to either 0.25 or 1 Gy of neutron or 1 or 4 Gy x-ray radiation were sacrificed at 1 or 7 days after exposure. Whole genome microarray analysis identified 7285 and 5045 differentially expressed genes in the blood of mice exposed to neutron or x-ray radiation, respectively. Neutron exposure resulted in mostly downregulated genes, whereas x-rays showed both down- and up-regulated genes. A total of 34 differentially expressed genes were regulated in response to all ≥1 Gy exposures at both times. Of these, 25 genes were consistently downregulated at days 1 and 7, whereas 9 genes, including the transcription factor E2f2, showed bi-directional regulation; being downregulated at day 1, while upregulated at day 7. Gene ontology analysis revealed that genes involved in nucleic acid metabolism processes were persistently downregulated in neutron irradiated mice, whereas genes involved in lipid metabolism were upregulated in x-ray irradiated animals. Most biological processes significantly enriched at both timepoints were consistently represented by either under- or over-expressed genes. In contrast, cell cycle processes were significant among down-regulated genes at day 1, but among up-regulated genes at day 7 after exposure to either neutron or x-rays. Cell cycle genes downregulated at day 1 were mostly distinct from the cell cycle genes upregulated at day 7. However, five cell cycle genes, Fzr1, Ube2c, Ccna2, Nusap1, and Cdc25b, were both downregulated at day 1 and upregulated at day 7.ConclusionsWe describe, for the first time, the gene expression profile of mouse blood cells following exposure to neutrons. We have found that neutron radiation results in both distinct and common gene expression patterns compared with x-ray radiation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3436-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Comparison of gene expression response to neutron and x-ray irradiation using mouse blood

Broustas

Harken

et al. 2017

BMC Genomics

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“…Cells overexpressing UBE2C ignore the mitotic spindle checkpoint signals and lose genomic stability, which leads to cancer and poor prognosis in many cancers. Our previous studies have shown UBE2C to be a potential target for treatment in cervical cancer [8–10]. …”

Section: Discussionmentioning

confidence: 99%

“…We have also shown that a 7 gene signature which includes UBE2C could be useful to identify patients who can be treated with radiotherapy alone [9]. Functional studies inhibiting UBE2C was found to enhance radiation and chemo-sensitivity in cervical cancer cell lines [10]. UBE2C has been shown to be preferentially over expressed in cancers compared to 17 other E2 genes [7].…”

Section: Introductionmentioning

confidence: 99%

Identification of small molecule inhibitors against UBE2C by using docking studies

Sabitha

Rajkumar²

2012

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An increased expression of UBE2C (Ubiquitin-conjugating enzyme E2C) has been associated with high tumor grade and cancer progression. It is an essential indicator of the mitotic destruction events. Our microarray study on cervical cancers showed UBE2C to be over expressed in cervical cancer. Subsequent studies from our laboratory, showed that inhibition of UBE2C can enhance radiation and chemosensitivity. Therefore it can be an appropriate target for drug development to identify potential and specific inhibitor of cancer. To identify small molecule inhibitors, a computational approach was used to model UBE2C and further docking studies were carried out. Different ligand subsets such as ChemBank, PDB, KEGG, Drug-likeness NCI, Not annotated NCI of ligand library ligands were downloaded and docked with UBE2C. Schrodinger tools were used for identifying active sites and docking studies of ligands with UBE2C. Based on glide score, the potential ligands were screened and its interaction with UBE2C was identified. We also analyzed the drug like properties such as absorption, distribution, metabolism, excretion and toxicity (ADME/T) of docked compounds. Our results suggest that 2,4-diimino-1-methyl-1,3,5-triazepan-6-one, sulfuric acid compound with 5,6-diamino-2,4-pyrimidinediol (1:1) and 7-alpha-d-ribofuranosyl-2-aminopurine-5'-phosphate may act as best inhibitors and further in vitro studies, may lead to development of novel and best inhibitor of UBE2C.

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“…These results suggest that UBE2C aberrant UbcH10 expression leads to chromosomal instability and further indicate UBE2C is a potential trigger for the initiation of cancer. Substantial evidence has showed abnormal high UBE2C was observed in various human solid cancers including esophageal adenocarcinoma, thyroid cancer, colon cancer, ovarian cancer, breast cancer, hepatocellular carcinoma, and cervix cancer (pallante et al, 2005;Lin et al, 2006;Berlingieri et al, 2007a;2007b;Ieta et al, 2007;Chen et al, 2010;Bose et al, 2012). In colorectal cancer cells, Bavi et al found UBE2C overexpression promoted cellular proliferation, whereas depletion of UBE2C expression suppressed growth of cells (Bavi et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Effects of Ubiquitin-conjugating Enzyme 2C on Invasion, Proliferation and Cell Cycling of Lung Cancer Cells

Tang¹,

Wang²,

Tang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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The aims of this study were to investigate the influence of ubiquitin-conjugating enzyme E2C (UBE2C) on biological behavior of lung cancer cells. Using MTT, flow cytometry and invasion assays, we detected UBE2C expression and evaluated its biological properties in these cells, including effects on proliferation, the cell cycle profile and invasive capability. Compared with control cells, the UBE2C transfected cells demonstrated increased cellular proliferation (p<0.05). UBE2C transfected cells also had a lower percentage in G1 phase and a higher percentage in S phase (p<0.05). Importantly, the UBE2C transfected cells had a notable enhancement of cell numbers penetrating the basement membrane compared with the control group (p<0.05). Ectopic upregulation UBE2C promoted the growth of lung cancer cells in vivo. Furthermore, we found UBE2C increased the expression of cyclin D1 and MMP-2. These results show UBE2C may represent a potential therapeutic target for lung cancer.

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Dominant negative Ubiquitin-conjugating enzyme E2C sensitizes cervical cancer cells to radiation

Abstract: These results suggested that the Ubiquitin-conjugating enzyme E2C (UBE2C) gene is a potential therapeutic target for cervical cancer treatment.

Cited by 16 publications

References 17 publications

Comparison of gene expression response to neutron and x-ray irradiation using mouse blood

Comparison of gene expression response to neutron and x-ray irradiation using mouse blood

Identification of small molecule inhibitors against UBE2C by using docking studies

Effects of Ubiquitin-conjugating Enzyme 2C on Invasion, Proliferation and Cell Cycling of Lung Cancer Cells

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