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Francesco Morra, Francesco Merolla, Virginia Napolitano, Gennaro Ilardi, Caterina Miro, Simona Paladino, Stefania Staibano, Aniello Cerrato, Angela Celetti
PURPOSE OF THE STUDY: Reduced levels of the tumor suppressor protein CCDC6 sensitize cancer cells to the treatment with PARP-inhibitors. The turnover of CCDC6 protein is regulated by the de-ubiquitinase USP7, which also controls the androgen receptor (AR) stability. Here, we correlated the expression levels of CCDC6 and USP7 proteins in primary prostate cancers (PC). Moreover, we tested the efficacy of the USP7 inhibitors, in combination with PARP-inhibitors as a novel therapeutic option in advanced prostate cancer...
March 22, 2017: Oncotarget
Rui Wang, Yue Song, Xi Liu, Qixue Wang, Yunfei Wang, Liwei Li, Chunsheng Kang, Qingyu Zhang
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...
April 2017: International Journal of Oncology
Constantinos G Broustas, Yanping Xu, Andrew D Harken, Guy Garty, Sally A Amundson
BACKGROUND: In 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. RESULTS: Mice exposed to either 0...
January 3, 2017: BMC Genomics
Malwina Michalak, Uwe Warnken, Sabine André, Martina Schnölzer, Hans-Joachim Gabius, Juergen Kopitz
Endogenous lectins have the capacity to translate glycan-encoded information on the cell surface into effects on cell growth. As test cases to examine changes in protein presence associated with tumor growth inhibition, we applied SILAC-based proteomics on human colon carcinoma cells treated with galectin-4 (Gal-4). The five tested lines-LS 180, Vaco 432, Colo 205, CX 1, and HCT 116-responded with differentiation and reduced proliferation to Gal-4 binding. In proteomic analysis (mass spectral data deposited with PRIDE, PXD003489), 2654 proteins were quantified, of which 190 were down-regulated and 115 were up-regulated (>2-fold)...
December 2, 2016: Journal of Proteome Research
Elisabetta Bigagli, Carlotta De Filippo, Cinzia Castagnini, Simona Toti, Francesco Acquadro, Francesco Giudici, Marilena Fazi, Piero Dolara, Luca Messerini, Francesco Tonelli, Cristina Luceri
BACKGROUND: DNA copy number alterations (CNAs) and gene expression changes have amply been encountered in colorectal cancers (CRCs), but the extent at which CNAs affect gene expression, as well as their relevance for tumor development, are still poorly defined. Here we aimed at assessing the clinical relevance of these parameters in a 10 year follow-up study. METHODS: Tumors and normal adjacent colon mucosa, obtained at primary surgery from 21 CRC patients, were subjected to (i) high-resolution array CGH (a-CGH) for the detection of CNAs and (ii) microarray-based transcriptome profiling for the detection of gene expression (GE) changes...
December 2016: Cellular Oncology (Dordrecht)
Dimitriya H Garvanska, Marie Sofie Yoo Larsen, Jakob Nilsson
The spindle assembly checkpoint (SAC) inhibits the anaphase-promoting complex/cyclosome (APC/C) in response to unattached kinetochores by generating a diffusible inhibitor termed the mitotic checkpoint complex (MCC). At metaphase, rapid activation of the APC/C requires removal of the MCC, a process that has been shown to depend on the APC/C E2 enzymes, UBE2C and UBE2S. Here we investigate the in vivo role of the APC/C E2 enzymes in SAC silencing using CRISPR/Cas9 genetically engineered HCT116 UBE2C or UBE2S null cell lines...
October 15, 2016: Biology Open
Antonio Palumbo, Nathalia Meireles Da Costa, Marco De Martino, Romina Sepe, Simona Pellecchia, Vanessa Paiva Leite de Sousa, Pedro Nicolau Neto, Cleber Dario Kruel, Anke Bergman, Luiz Eurico Nasciutti, Alfredo Fusco, Luis Felipe Ribeiro Pinto
The esophageal squamous cell carcinoma (ESCC) is widely known as a highly lethal and poor understood cancer, then requiring the search for novel molecular markers to improve its management and patients survival. Recently, ubiquitin-conjugating enzyme E2C (UBE2C) has been figuring as a prominent tumor biomarker candidate, once it has been recognized as a key player in cell cycle progression. In this way, the aim of this study was to evaluate the expression profile of UBE2C gene and protein in ESCC samples, as well as its diagnostic and prognostic marker potential, and its contribution to ESSC genesis and/or progression by performing in vitro functional assays...
October 4, 2016: Oncotarget
Wei Wang, Zhiwei Wang, Jun Zhao, Min Wei, Xinghua Zhu, Qi He, Tianlong Ling, Xiaoyan Chen, Ziang Cao, Yixin Zhang, Lei Liu, Minxin Shi
Current prognostic factors fail to accurately determine prognosis for patients with esophageal squamous cell carcinoma (ESCC) after surgery. Here, we constructed a survival prediction model for prognostication in patients with ESCC. Candidate molecular biomarkers were extracted from the Gene Expression Omnibus (GEO), and Cox regression analysis was performed to determine significant prognostic factors. The survival prediction model was constructed based on cluster and discriminant analyses in a training cohort (N=205), and validated in a test cohort (N=207)...
September 27, 2016: Oncotarget
Chan Ho Lee, Ja Yoon Ku, Jung Min Ha, Sun Sik Bae, Jeong Zoo Lee, Choung-Soo Kim, Hong Koo Ha
PURPOSE: This study is designed to identify the androgen receptor variant 7 (AR-V7) status, clinical significance of AR-V7 in hormone sensitive prostate cancer (HSPC). Then, we evaluated AR-V7 and changes of its target gene, ubiquitin-conjugating enzyme E2C (UBE2C) which is an anaphase-promoting complex/cyclosome (APC/C)-specific ubiquitin-conjugating enzyme, in castration-resistant prostate cancer (CRPC) in serial tumor biopsies from patients receiving androgen deprivation therapy. METHODS: We used RT-PCR and Q-PCR assay to evaluate AR-V7, androgen receptor full length (AR-FL), and UBE2C in tumor biopsies from patients with HSPC and CRPC...
January 2017: Prostate
Won Tae Kim, Pildu Jeong, Chunri Yan, Ye Hwan Kim, Il-Seok Lee, Ho-Won Kang, Yong-June Kim, Sang-Cheol Lee, Sang Jin Kim, Yong Tae Kim, Sung-Kwon Moon, Yung-Hyun Choi, Isaac Yi Kim, Seok Joong Yun, Wun-Jae Kim
BACKGROUND: There is growing interest in circulating nucleic acids as cancer detection biomarkers. Therefore, the aim of the present study was to identify a key urinary cell-free RNA marker that may assist in the diagnosis of BC. RESULTS: Five cell-free RNAs were selected as candidate cell-free RNAs from tissue microarray data. An area under the curve (AUC) cut-off value of 0.7 in receiver operating characteristic (ROC) curve analysis identified four urinary cell-free RNAs for further analysis (CDC20, ESM1, UBE2C, and CA9; AUC = 0...
September 6, 2016: Oncotarget
Masaya Yamaguchi, Ryan VanderLinden, Florian Weissmann, Renping Qiao, Prakash Dube, Nicholas G Brown, David Haselbach, Wei Zhang, Sachdev S Sidhu, Jan-Michael Peters, Holger Stark, Brenda A Schulman
The mitotic checkpoint complex (MCC) coordinates proper chromosome biorientation on the spindle with ubiquitination activities of CDC20-activated anaphase-promoting complex/cyclosome (APC/C(CDC20)). APC/C(CDC20) and two E2s, UBE2C and UBE2S, catalyze ubiquitination through distinct architectures for linking ubiquitin (UB) to substrates and elongating polyUB chains, respectively. MCC, which contains a second molecule of CDC20, blocks APC/C(CDC20)-UBE2C-dependent ubiquitination of Securin and Cyclins, while differentially determining or inhibiting CDC20 ubiquitination to regulate spindle surveillance, checkpoint activation, and checkpoint termination...
August 18, 2016: Molecular Cell
Jeri Kim, John W Davis, Eric A Klein, Cristina Magi-Galluzzi, Yair Lotan, John F Ward, Louis L Pisters, Joseph W Basler, Curtis A Pettaway, Andrew Stephenson, Elsa M Li Ning Tapia, Eleni Efstathiou, Xuemei Wang, Kim-Anh Do, J Jack Lee, Ivan P Gorlov, Lana A Vornik, Ashraful M Hoque, Ina N Prokhorova, Howard L Parnes, Scott M Lippman, Ian M Thompson, Powel H Brown, Christopher J Logothetis, Patricia Troncoso
BACKGROUND: In the Prostate Cancer Prevention Trial, finasteride selectively suppressed low-grade prostate cancer and significantly reduced the incidence of prostate cancer in men treated with finasteride compared with placebo. However, an apparent increase in high-grade disease was also observed among men randomized to finasteride. We aimed to determine why and hypothesized that there is a grade-dependent response to finasteride. METHODS: From 2007 to 2012, we randomized dynamically by intranet-accessible software 183 men with localized prostate cancer to receive 5mg finasteride or placebo daily in a double-blind study during the 4-6weeks preceding prostatectomy...
May 2016: EBioMedicine
Nicholas G Brown, Ryan VanderLinden, Edmond R Watson, Florian Weissmann, Alban Ordureau, Kuen-Phon Wu, Wei Zhang, Shanshan Yu, Peter Y Mercredi, Joseph S Harrison, Iain F Davidson, Renping Qiao, Ying Lu, Prakash Dube, Michael R Brunner, Christy R R Grace, Darcie J Miller, David Haselbach, Marc A Jarvis, Masaya Yamaguchi, David Yanishevski, Georg Petzold, Sachdev S Sidhu, Brian Kuhlman, Marc W Kirschner, J Wade Harper, Jan-Michael Peters, Holger Stark, Brenda A Schulman
Protein ubiquitination involves E1, E2, and E3 trienzyme cascades. E2 and RING E3 enzymes often collaborate to first prime a substrate with a single ubiquitin (UB) and then achieve different forms of polyubiquitination: multiubiquitination of several sites and elongation of linkage-specific UB chains. Here, cryo-EM and biochemistry show that the human E3 anaphase-promoting complex/cyclosome (APC/C) and its two partner E2s, UBE2C (aka UBCH10) and UBE2S, adopt specialized catalytic architectures for these two distinct forms of polyubiquitination...
June 2, 2016: Cell
Cong Li, Wentao Cai, Chenghao Zhou, Hongwei Yin, Ziqi Zhang, Juan J Loor, Dongxiao Sun, Qin Zhang, Jianfeng Liu, Shengli Zhang
Paired-end RNA sequencing (RNA-Seq) was used to explore the bovine transcriptome from the mammary tissue of 12 Chinese Holstein cows with 6 extremely high and 6 low phenotypic values for milk protein percentage. We defined the differentially expressed transcripts between the two comparison groups, extremely high and low milk protein percentage during the peak lactation (HP vs LP) and during the non-lactating period (HD vs LD), respectively. Within the differentially expressed genes (DEGs), we detected 157 at peak lactation and 497 in the non-lactating period with a highly significant correlation with milk protein concentration...
2016: Scientific Reports
Swati Bajaj, Sk Kayum Alam, Kumar Singha Roy, Arindam Datta, Somsubhra Nath, Susanta Roychoudhury
Spindle assembly checkpoint governs proper chromosomal segregation during mitosis to ensure genomic stability. At the cellular level, this event is tightly regulated by UBE2C, an E2 ubiquitin-conjugating enzyme that donates ubiquitin to the anaphase-promoting complex/cyclosome. This, in turn, facilitates anaphase-onset by ubiquitin-mediated degradation of mitotic substrates. UBE2C is an important marker of chromosomal instability and has been associated with malignant growth. However, the mechanism of its regulation is largely unexplored...
July 1, 2016: Journal of Biological Chemistry
Ruimin Ma, Xixiong Kang, Guojun Zhang, Fang Fang, Yamei DU, Hong Lv
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...
March 2016: Oncology Letters
Thomas Wild, Marie Sofie Yoo Larsen, Takeo Narita, Julie Schou, Jakob Nilsson, Chunaram Choudhary
The anaphase-promoting complex/cyclosome (APC/C) and the spindle assembly checkpoint (SAC), which inhibits the APC/C, are essential determinants of mitotic timing and faithful division of genetic material. Activation of the APC/C is known to depend on two APC/C-interacting E2 ubiquitin-conjugating enzymes-UBE2C and UBE2S. We show that APC/C activity in human cells is tuned by the combinatorial use of three E2s, namely UBE2C, UBE2S, and UBE2D. Genetic deletion of UBE2C and UBE2S, individually or in combination, leads to discriminative reduction in APC/C function and sensitizes cells to UBE2D depletion...
March 1, 2016: Cell Reports
Melissa Schmidt, Andreas Mock, Christine Jungk, Felix Sahm, Anna Theresa Ull, Rolf Warta, Katrin Lamszus, Konstantinos Gousias, Ralf Ketter, Saskia Roesch, Carmen Rapp, Sebastian Schefzyk, Steffi Urbschat, Bernd Lahrmann, Almuth F Kessler, Mario Löhr, Christian Senft, Niels Grabe, David Reuss, Philipp Beckhove, Manfred Westphal, Andreas von Deimling, Andreas Unterberg, Matthias Simon, Christel Herold-Mende
Meningiomas are frequent central nervous system tumors. Although most meningiomas are benign (WHO grade I) and curable by surgery, WHO grade II and III tumors remain therapeutically challenging due to frequent recurrence. Interestingly, relapse also occurs in some WHO grade I meningiomas. Hence, we investigated the transcriptional features defining aggressive (recurrent, malignantly progressing or WHO grade III) meningiomas in 144 cases. Meningiomas were categorized into non-recurrent (NR), recurrent (R), and tumors undergoing malignant progression (M) in addition to their WHO grade...
March 22, 2016: Oncotarget
Minoru Kato, Carmen A Banuelos, Yusuke Imamura, Jacky K Leung, Daniel P Caley, Jun Wang, Nasrin R Mawji, Marianne D Sadar
PURPOSE: The PI3K/Akt/mTOR pathway is activated in most castration-resistant prostate cancers (CRPC). Transcriptionally active androgen receptor (AR) plays a role in the majority of CRPCs. Therefore, cotargeting full-length (FL) AR and PI3K/Akt/mTOR signaling has been proposed as a possible, more effective therapeutic approach for CRPC. However, truncated AR-splice variants (AR-V) that are constitutively active and dominant over FL-AR are associated with tumor progression and resistance mechanisms in CRPC...
June 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
M Y Yang, J E Fortune
The signals that regulate activation, a key transition in ovarian follicular development, are still not well understood, especially in nonrodent species. To gain insight into the regulation of this transition in cattle, we combined a microarray approach with an in vitro system in which ovarian cortical pieces cultured in control medium are enriched for primordial follicles, whereas pieces cultured with insulin are enriched for primary follicles. Total RNA was extracted from cultured cortical pieces, and then transcripts were identified and analyzed using the Affymetrix Bovine Genome GeneChip array...
December 2015: Physiological Genomics
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