Ubiquitin-Conjugating Enzyme UBE2C Is Highly Expressed in Breast Microcalcification Lesions

Chou, Chen Pin; Huang, Nan Chieh; Jhuang, Shu Jhen; Pan, Huay‐Ben; Peng, Nan; Cheng, Jiin Tsuey; Chen, Chian Feng; Chen, Jih Jung; Chang, Tsun-Hsu

doi:10.1371/journal.pone.0093934

Cited by 44 publications

(51 citation statements)

References 38 publications

(41 reference statements)

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“…WST-1 assay (Roche, Basel, Switzerland) was used to monitor cell proliferation (42, 43); H292 cells were trypsinized and resuspended in culture medium, then plated at 5 × 10 3 cells per well in 96-well plates and incubated overnight. After LPS treatment followed by polyI:C transfection, cells were incubated with 10 μl WST-1 reagent for 2 h. The cell viability was quantified by multi-well spectrophotometry (Anthos, Biochrom, Cambridge, UK).…”

Section: Methodsmentioning

confidence: 99%

Lipopolysaccharide Attenuates Induction of Proallergic Cytokines, Thymic Stromal Lymphopoietin, and Interleukin 33 in Respiratory Epithelial Cells Stimulated with PolyI:C and Human Parechovirus

Lin

Cheng

et al. 2016

Front. Immunol.

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Epidemiological studies based on the “hygiene hypothesis” declare that the level of childhood exposure to environmental microbial products is inversely related to the incidence of allergic diseases in later life. Multiple types of immune cell-mediated immune regulation networks support the hygiene hypothesis. Epithelial cells are the first line of response to microbial products in the environment and bridge the innate and adaptive immune systems; however, their role in the hygiene hypothesis is unknown. To demonstrate the hygiene hypothesis in airway epithelial cells, we examined the effect of lipopolysaccharide (LPS; toll-like receptor 4 ligand) on the expression of the proallergic cytokines thymic stromal lymphopoietin (TSLP) and interleukin 33 (IL33) in H292 cells (pulmonary mucoepidermoid carcinoma cells). Stimulation with the TLR ligand polyI:C and human parechovirus type 1 (HPeV1) but not LPS-induced TSLP and IL33 through interferon regulatory factor 3 (IRF3) and NF-κB activity, which was further validated by using inhibitors (dexamethasone and Bay 11-7082) and short hairpin RNA-mediated gene knockdown. Importantly, polyI:C and HPeV1-stimulated TSLP and IL33 induction was reduced by LPS treatment by attenuating TANK-binding kinase 1, IRF3, and NF-κB activation. Interestingly, the basal mRNA levels of TLR signaling proteins were downregulated with long-term LPS treatment of H292 cells, which suggests that such long-term exposure modulates the expression of innate immunity signaling molecules in airway epithelial cells to mitigate the allergic response. In contrast to the effects of LPS treatment, the alarmin high-mobility group protein B1 acts in synergy with polyI:C to promote TSLP and IL33 expression. Our data support part of the hygiene hypothesis in airway epithelia cells in vitro. In addition to therapeutic targeting of TSLP and IL33, local application of non-pathogenic LPS may be a rational strategy to prevent allergies.

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Section: Methodsmentioning

confidence: 99%

Lipopolysaccharide Attenuates Induction of Proallergic Cytokines, Thymic Stromal Lymphopoietin, and Interleukin 33 in Respiratory Epithelial Cells Stimulated with PolyI:C and Human Parechovirus

Lin

Cheng

et al. 2016

Front. Immunol.

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“…Interestingly, UBE2C is nearly undetectable in normal tissues, at both the RNA or protein levels. In contrast, increasing evidence indicates that UBE2C protein is overexpressed in many human tumor types, including brain tumors (10), malignant breast carcinomas (11), lung cancer (12,13), anaplastic thyroid carcinomas (14), esophageal adenocarcinomas (15), hepatocellular carcinomas (16) and colorectal cancer (17–19), suggesting that UBE2C may play an important role in tumorigenesis and progression. UBE2C overexpression causes the centrosome duplication instability, and variety of proteins can cause this phenomenon, including the anaphase-promoting complex (APC/C) substrates cyclin B, AURKA and PLK1 (20,21).…”

Section: Introductionmentioning

confidence: 99%

UBE2C induces EMT through Wnt/β-catenin and PI3K/Akt signaling pathways by regulating phosphorylation levels of Aurora-A

Wang

Song

Liu

et al. 2017

International Journal of Oncology

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The ubiquitin-conjugating enzyme 2C (UBE2C) is the key component in the ubiquitin proteasome system (UPS) by partnering with the anaphase-promoting complex (APC/C). A high UBE2C protein expression level has been reported in various types of human tumors. However, little is known about the precise mechanism by which UBE2C expression is downregulated in gastric cancer. We found in MGC-803 and SGC-7901 gastric cancer cells UBE2C-deficient G2/M phase arrest in the cell cycle and subsequently decreased gastric adenocarcinoma tumorigenesis. In the previous study, we identified Aurora-A (AURKA) as the hub gene of the gastric cancer linkage network based genome-wide association study (eGWAS). Furthermore, knockdown of UBE2C using siRNA markedly reduced the level of phosphorylation AURKA (p-AURKA) via Wnt/β-catenin and PI3K/Akt signaling pathways suppressed the occurrence and development of gastric cancer. Additionally, the expression of E-cadherin was up-regulated and N-cadherin was down-regulated in response to UBE2C knockdown and inhibits epithelial-mesenchymal transition (EMT). Collectively, our data suggest that the activity of AURKA might be regulated by UBE2C through regulating the activity of APC/C. UBE2C may be a new marker in the diagnosis of gastric cancer and may be a potential therapeutic target for the treatment of gastric adenocarcinoma.

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“…They circumvent the frequent lack of concordance between mRNA and protein expression (21,22) and could reveal biomarkers of PDAC tumor cell drug sensitivity, which genomic and transcriptomic profiling has been unable to provide (7). A unique ion current-based proteomics strategy was an important enabling factor in this study, in that it permits reproducible and reliable quantification of the large number of samples required for comprehensive temporal analysis of cellular drug responses (23,24), provides extremely-low levels of missing data (15) and the ability to quantify subtle changes in protein abundance (15,25), and has well-controlled falsepositive discovery rates (26,27). Using this strategy, we performed quantitative proteomic analysis of PDAC cells treated with birinapant and paclitaxel, alone and in combination.…”

Section: Birinapant (Tl32711) Is a Bivalent Second Mitochondrial-derimentioning

confidence: 99%

Temporal Effects of Combined Birinapant and Paclitaxel on Pancreatic Cancer Cells Investigated via Large-Scale, Ion-Current-Based Quantitative Proteomics (IonStar)

Wang

Niu

Li³

et al. 2018

Molecular & Cellular Proteomics

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SummaryDespite decades of effort, pancreatic adenocarcinoma (PDAC) remains an intractable clinical challenge.An insufficient understanding of mechanisms underlying tumor cell responses to chemotherapy contributes significantly to the lack of effective treatment regimens. Here, paclitaxel, a first-line chemotherapeutic agent, was observed to interact synergistically with birinapant, a Second Mitochondrial-derived Activator of Caspases mimetic. Therefore, we investigated molecular-level drug interaction mechanisms using comprehensive, reproducible, and well-controlled ion-current-based MS1 quantification (IonStar). By analyzing 40 biological samples in a single batch, we compared temporal proteomic responses of PDAC cells treated with birinapant and paclitaxel, alone and combined. Using stringent criteria (e.g. strict false-discovery-rate FDR control, 2 peptides/protein), we quantified 4069 unique proteins confidently (99.8% without any missing data), and 541 proteins were significantly altered in the three treatment groups, with a FDR of <1%. Interestingly, most of these proteins were altered only by combined birinapant/paclitaxel, and these predominantly represented three biological processes: mitochondrial function, cell growth and apoptosis, and cell cycle arrest. Proteins responsible for activation of oxidative phosphorylation, fatty acid β-oxidation, and inactivation of aerobic glycolysis were altered largely by combined birinapant/paclitaxel compared to single drugs, suggesting the Warburg effect, which is critical for survival and proliferation of cancer cells, was alleviated by the combination treatment. Metabolic profiling was performed to confirm substantially greater suppression of the Warburg effect by the combined agents compared to either drug alone. Immunoassays confirmed proteomic data revealing changes in apoptosis/survival signaling pathways, such as inhibition of PI3K/AKT, JAK/STAT, and MAPK/ERK signal transduction, as well as induction of G2/M arrest, and showed the drug combination induced much more apoptosis than did single agents. Overall, this in-depth, large-scale proteomics study provided novel insights into molecular mechanisms underlying synergy of combined birinapant/paclitaxel, and describes a proteomics/informatics pipeline that can be applied broadly to the development of cancer drug combination regimens.4

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Ubiquitin-Conjugating Enzyme UBE2C Is Highly Expressed in Breast Microcalcification Lesions

Cited by 44 publications

References 38 publications

Lipopolysaccharide Attenuates Induction of Proallergic Cytokines, Thymic Stromal Lymphopoietin, and Interleukin 33 in Respiratory Epithelial Cells Stimulated with PolyI:C and Human Parechovirus

Lipopolysaccharide Attenuates Induction of Proallergic Cytokines, Thymic Stromal Lymphopoietin, and Interleukin 33 in Respiratory Epithelial Cells Stimulated with PolyI:C and Human Parechovirus

UBE2C induces EMT through Wnt/β-catenin and PI3K/Akt signaling pathways by regulating phosphorylation levels of Aurora-A

Temporal Effects of Combined Birinapant and Paclitaxel on Pancreatic Cancer Cells Investigated via Large-Scale, Ion-Current-Based Quantitative Proteomics (IonStar)

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