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Min Wu, Zhaobo Liu, Aiying Zhang, Ning Li
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide. However, the precise mechanisms of the development and progression of HCC remain unclear. The present study attempted to identify and functionally analyze the differentially expressed genes between HCC and cirrhotic tissues by using comprehensive bioinformatics analyses. METHODS: The GSE63898 gene expression profile was downloaded from the Gene Expression Omnibus (GEO) and analyzed using the online tool GEO2R to identify differentially expressed genes (DEGs)...
February 2019: Medicine (Baltimore)
Yan Wu, Dan Jin, Xiaohong Wang, Jing Du, Weihua Di, Jiajia An, Cuijie Shao, Jiwei Guo
Objectives: Cisplatin (DDP) is one of the most commonly used chemotherapeutic drugs for several cancers, including non-small-cell lung cancer (NSCLC). However, resistance to DDP eventually develops, limiting its further application. New therapy targets are urgently needed to reverse DDP resistance. Methods: The mRNA expression of UBE2C , ZEB1/2 , ABCG2 , and ERCC1 was analyzed by reverse transcription-polymerase chain reaction. The protein levels of these molecules were analyzed by Western blotting and immunofluorescent staining...
2019: Journal of Oncology
Maria V Luna Velez, Gerald W Verhaegh, Frank Smit, J P Michiel Sedelaar, Jack A Schalken
One of the mechanisms by which advanced prostate cancer develops resistance to androgen deprivation therapy is the elevated expression of C-terminally truncated androgen receptor (AR) variants. These variants, such as AR-V7, originate from aberrant splicing of the AR pre-mRNA and the inclusion of a cryptic exon containing a premature stop codon in the mRNA. The resulting loss of the ligand-binding domain allows AR-V7 to act as a constitutively active transcription factor. Here, we designed two antisense oligonucleotides (AONs) directed against cryptic splicing signals within the AR pre-mRNA...
January 21, 2019: Oncogene
Simple Mohanta, Samanta Sekhar Khora, Amritha Suresh
OBJECTIVE: This study aimed to identify the cancer stem cell specific biomarkers that can be effective candidate prognosticators of oral squamous cell carcinoma. DESIGN: Microarray-based meta-analysis derived transcriptional profile of head and neck cancers was compared with the Cancer Stem Cell database to arrive at a subset of markers. This subset was further co-related with clinico-pathological parameters, recurrence and survival of oral cancer patients (n = 313) in The Cancer Genome Atlas database and in oral cancer (n = 28) patients...
January 4, 2019: Archives of Oral Biology
Joan Fernandez Esmerats, Nicolas Villa-Roel, Sandeep Kumar, Lina Gu, Md Tausif Salim, Michael Ohh, W Robert Taylor, Robert M Nerem, Ajit P Yoganathan, Hanjoong Jo
Objective- Calcific aortic valve (AV) disease, characterized by AV sclerosis and calcification, is a major cause of death in the aging population; however, there are no effective medical therapies other than valve replacement. AV calcification preferentially occurs on the fibrosa side, exposed to disturbed flow (d-flow), whereas the ventricularis side exposed to predominantly stable flow remains protected by unclear mechanisms. Here, we tested the role of novel flow-sensitive UBE2C (ubiquitin E2 ligase C) and microRNA-483-3p (miR-483) in flow-dependent AV endothelial function and AV calcification...
January 3, 2019: Arteriosclerosis, Thrombosis, and Vascular Biology
Xin Gao, Yinyi Chen, Mei Chen, Shunlan Wang, Xiaohong Wen, Shufang Zhang
Background: Bladder cancer is a malignant tumor in the urinary system with high mortality and recurrence rates. However, the causes and recurrence mechanism of bladder cancer are not fully understood. In this study, we used integrated bioinformatics to screen for key genes associated with the development of bladder cancer and reveal their potential molecular mechanisms. Methods: The GSE7476, GSE13507, GSE37815 and GSE65635 expression profiles were downloaded from the Gene Expression Omnibus database, and these datasets contain 304 tissue samples, including 81 normal bladder tissue samples and 223 bladder cancer samples...
2018: PeerJ
Giorgia Simonetti, Antonella Padella, Italo Farìa do Valle, Maria Chiara Fontana, Eugenio Fonzi, Samantha Bruno, Carmen Baldazzi, Viviana Guadagnuolo, Marco Manfrini, Anna Ferrari, Stefania Paolini, Cristina Papayannidis, Giovanni Marconi, Eugenia Franchini, Elisa Zuffa, Maria Antonella Laginestra, Federica Zanotti, Annalisa Astolfi, Ilaria Iacobucci, Simona Bernardi, Marco Sazzini, Elisa Ficarra, Jesus Maria Hernandez, Peter Vandenberghe, Jan Cools, Lars Bullinger, Emanuela Ottaviani, Nicoletta Testoni, Michele Cavo, Torsten Haferlach, Gastone Castellani, Daniel Remondini, Giovanni Martinelli
BACKGROUND: Aneuploidy occurs in more than 20% of acute myeloid leukemia (AML) cases and correlates with an adverse prognosis. METHODS: To understand the molecular bases of aneuploid acute myeloid leukemia (A-AML), this study examined the genomic profile in 42 A-AML cases and 35 euploid acute myeloid leukemia (E-AML) cases. RESULTS: A-AML was characterized by increased genomic complexity based on exonic variants (an average of 26 somatic mutations per sample vs 15 for E-AML)...
November 27, 2018: Cancer
Yasuomi Shimizu, Satoshi Tamada, Minoru Kato, Yukiyoshi Hirayama, Yuji Takeyama, Taro Iguchi, Marianne D Sadar, Tatsuya Nakatani
Expression of androgen receptor (AR) splice variant 7 (AR-V7) has been identified as the mechanism associated with the development of castration-resistant prostate cancer (CRPC). However, a potential link between AR-V7 expression and resistance to taxanes, such as docetaxel or cabazitaxel, has not been unequivocally demonstrated. To address this, we used LNCaP95-DR cells, which express AR-V7 and exhibit resistance to enzalutamide and docetaxel. Interestingly, LNCaP95-DR cells showed cross-resistance to cabazitaxel...
November 16, 2018: Journal of Clinical Medicine
Amro Aboukameel, Irfana Muqbil, Erkan Baloglu, William Senapedis, Yosef Landesman, Christian Argueta, Michael Kauffman, Hua Chang, Trinayan Kashyap, Sharon Shacham, Jasper E Neggers, Dirk Daelemans, Elisabeth I Heath, Asfar S Azmi
Emerging studies have shown that the expression of AR splice variants (ARv) lacking ligand-binding domain is associated with castrate-resistant prostate cancer (CRPC) and higher risk of tumor metastasis and recurrence. Nuclear export protein XPO1 regulates the nuclear localization of many proteins including tumor suppressor proteins. Increased XPO1 in prostate cancer is associated with a high Gleason score and bone metastasis. In this study, we found that high expression of AR splice variant 7 (AR-v7) was correlated with increased XPO1 expression...
October 19, 2018: Oncotarget
Mengwei Ni, Xinkui Liu, Jiarui Wu, Dan Zhang, Jinhui Tian, Ting Wang, Shuyu Liu, Ziqi Meng, Kaihuan Wang, Xiaojiao Duan, Wei Zhou, Xiaomeng Zhang
Background and Objective: Non-small cell lung cancer (NSCLC) accounts for 80-85% of all patients with lung cancer and 5-year relative overall survival (OS) rate is less than 20%, so that identifying novel diagnostic and prognostic biomarkers is urgently demanded. The present study attempted to identify potential key genes associated with the pathogenesis and prognosis of NSCLC. Methods: Four GEO datasets (GSE18842, GSE19804, GSE43458, and GSE62113) were obtained from the Gene Expression Omnibus (GEO) database...
2018: Frontiers in Genetics
Guangda Yang, Qianya Chen, Jieming Xiao, Hailiang Zhang, Zhichao Wang, Xiangan Lin
Background: This study was performed to identify disease-related genes and analyze prognostic values in nonsmoking females with non-small cell lung carcinoma (NSCLC). Materials and methods: Gene expression profile GSE19804 was downloaded from the Gene Expression Omnibus (GEO) database and analyzed by using GEO2R. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used for the functional and pathway enrichment analysis. Then, the Search Tool for the Retrieval of Interacting Genes, Cytoscape, and Molecular Complex Detection were used to construct the protein-protein interaction (PPI) network and identify hub genes...
2018: Cancer Management and Research
Philip Friedlander, Kevin Wood, Karl Wassmann, Alan M Christenfeld, Nina Bhardwaj, William K Oh
BACKGROUND: Anti-CTLA-4 immune checkpoint blockade is associated with immune-related adverse events (irAEs). Grade 3-4 diarrhea/colitis is the most frequent irAE requiring treatment discontinuation. Predicting high-risk diarrhea/colitis patients may facilitate early intervention, limit irAE severity, and extend treatment duration. No biomarkers currently predict for anti-CTLA-4 immunotherapy related severe diarrhea. METHODS: Whole-blood was collected pre-treatment and 30 days post-treatment initiation from patients with stage III or IV unresectable melanoma who received 15 mg/kg tremelimumab at 90 day intervals in two clinical trials...
September 18, 2018: Journal for Immunotherapy of Cancer
Jiwei Guo, Dan Jin, Yan Wu, Lijuan Yang, Jing Du, Kaikai Gong, Weiwei Chen, Juanjuan Dai, Shuang Miao, Sichuan Xi
Cisplatin (DDP) resistance has become the leading cause of mortality in non-small cell lung cancer (NSCLC). miRNA dysregulation significantly contributes to tumor progression. In this study, we found that miR-495 was significantly downregulated in lung cancer tissue specimens. This study aimed to elucidate the functions, direct target genes, and molecular mechanisms of miR-495 in lung cancer. miR-495 downregulated its substrate UBE2C through direct interaction with UBE2C 3'- untranslated region. UBE2C is a proto-oncogene activated in lung cancer; however, its role in chemotherapeutic resistance is unclear...
August 23, 2018: EBioMedicine
Enrico Derenzini, Patrizia Mondello, Tatiana Erazo, Ana Portelinha, Yuxuan Liu, Mary Scallion, Zahra Asgari, John Philip, Patrick Hilden, Debora Valli, Alessandra Rossi, Hakim Djaballah, Ouathek Ouerfelli, Elisa de Stanchina, Venkatraman E Seshan, Ronald C Hendrickson, Anas Younes
The phosphatidylinositol 3 kinase (PI3K)-glycogen synthase kinase β (GSK3β) axis plays a central role in MYC-driven lymphomagenesis, and MYC targeting with bromodomain and extraterminal protein family inhibitors (BETi) is a promising treatment strategy in lymphoma. In a high-throughput combinatorial drug screening experiment, BETi enhance the antiproliferative effects of PI3K inhibitors in a panel of diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma cell lines. BETi or MYC silencing upregulates several PI3K pathway genes and induces GSK3β S9 inhibitory phosphorylation, resulting in increased β-catenin protein abundance...
August 21, 2018: Cell Reports
Jun Zhang, Xinyu Liu, Guanzhen Yu, Lei Liu, Jiejun Wang, Xiaoyu Chen, Yuhai Bian, Yuan Ji, Xiaoyan Zhou, Yinan Chen, Jun Ji, Zhen Xiang, Lei Guo, Jingyuan Fang, Yihong Sun, Hui Cao, Zhenggang Zhu, Yingyan Yu
This study explored potential biomarkers associated with Lauren classification of gastric cancer. We screened microarray datasets on gastric cancer with information of Lauren classification in gene expression omnibus (GEO) database, and compared differentially expressing genes between intestinal-type or diffuse-type gastric cancer. Four sets of microarray data (GSE2669, GSE2680, GDS3438, and GDS4007) were enrolled into analysis. By differential gene analysis, UBE2C, CDH1, CENPF, ERO1L, SCD, SOX9, CKS1B, SPP1, MMP11, and ANLN were identified as the top genes related to intestinal-type gastric cancer, and MGP, FXYD1, FAT4, SIPA1L2, MUC5AC, MMP15, RAB23, FBLN1, ANXA10, and ADH1B were genes related to diffuse-type gastric cancer...
2018: Frontiers in Pharmacology
Jiwei Guo, Yan Wu, Jing Du, Lijuan Yang, Weiwei Chen, Kaikai Gong, Juanjuan Dai, Shuang Miao, Dan Jin, Sichuan Xi
The roles of aberrantly regulated autophagy in human malignancy and the mechanisms that initiate and sustain the repression of autophagy in carcinogenesis are less well defined. Activation of the oncogene UBE2C and repression of autophagy are concurrently underlying the initiation, progression, and metastasis of lung cancer and exploration of essential association of UBE2C with autophagy will confer more options in searching novel molecular therapeutic targets in lung cancer. Here we report that aberrant activation of UBE2C in lung tumors from patients associates with adverse prognosis and enhances cell proliferation, clonogenicity, and invasive growth of NSCLC...
June 13, 2018: Oncogenesis
Xuehai Wang, Gang Li, Qingsong Luo, Chongzhi Gan
To uncover the genes associated with the development of esophageal squamous cell carcinoma (ESCC), an ESCC microarray dataset was used to identify genes differentially expressed between ESCC and normal control tissues. The dataset GSE17351 was downloaded from the Gene Expression Omnibus, containing 5 tumor esophageal mucosa samples and 5 adjacent normal esophageal mucosa samples from 5 male patients with ESCC. The differentially expressed genes (DEGs) were identified using the Linear Models for Microarray Data R package...
June 2018: Oncology Letters
Xiaozhen Liu, Gan Jin, Jiacheng Qian, Hongjian Yang, Hongchao Tang, Xuli Meng, Yongfeng Li
BACKGROUND: This study aimed to screen sensitive biomarkers for the efficacy evaluation of neoadjuvant chemotherapy in breast cancer. METHODS: In this study, Illumina digital gene expression sequencing technology was applied and differentially expressed genes (DEGs) between patients presenting pathological complete response (pCR) and non-pathological complete response (NpCR) were identified. Further, gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were then performed...
April 23, 2018: World Journal of Surgical Oncology
H-Q Zhang, G Zhao, B Ke, G Ma, G-L Liu, H Liang, L-R Liu, X-S Hao
OBJECTIVE: The ubiquitin-conjugating enzyme E2C (UBE2C) has been known as a crucial factor upregulated in various tumors. The functions of UBE2C is mainly involved in the pathway protein ubiquitination. This study investigates the expression of UBE2C in gastric cancers and its correlation with overall survival rate. MATERIALS AND METHODS: Real-time PCR (RT-PCR) and Western blotting were performed to determine the expression of UBE2C in gastric cancer samples and adjacent normal tissues...
March 2018: European Review for Medical and Pharmacological Sciences
Pedro Nicolau-Neto, Antonio Palumbo, Marco De Martino, Francesco Esposito, Tatiana de Almeida Simão, Alfredo Fusco, Luiz Eurico Nasciutti, Nathalia Meireles Da Costa, Luis Felipe Ribeiro Pinto
FOXM1 (forkhead box protein M1) is a transcription factor that participates in all stages of tumor development, mainly through the control of cell cycle and proliferation, regulating the expression of genes involved in G1/S and G2/M transition and M phase progression. The ubiquitin conjugating enzyme E2 (UBE2C) is a member of the anaphase promoting complex/cyclosome, promoting the degradation of several target proteins along cell cycle progression, during metaphase/anaphase transition. FOXM1 and UBE2C have been found overexpressed in a wide range of different solid tumors...
March 29, 2018: Genes
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