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cancer gene

Patrick McGillivray, Russell Ault, Mayur Pawashe, Robert Kitchen, Suganthi Balasubramanian, Mark Gerstein
Upstream open reading frames (uORFs) latent in mRNA transcripts are thought to modify translation of coding sequences by altering ribosome activity. Not all uORFs are thought to be active in such a process. To estimate the impact of uORFs on the regulation of translation in humans, we first circumscribed the universe of all possible uORFs based on coding gene sequence motifs and identified 1.3 million unique uORFs. To determine which of these are likely to be biologically relevant, we built a simple Bayesian classifier using 89 attributes of uORFs labeled as active in ribosome profiling experiments...
March 19, 2018: Nucleic Acids Research
Jennifer F Knight, Vanessa Y C Sung, Elena Kuzmin, Amber L Couzens, Danielle A de Verteuil, Colin D H Ratcliffe, Paula P Coelho, Radia M Johnson, Payman Samavarchi-Tehrani, Tina Gruosso, Harvey W Smith, Wontae Lee, Sadiq M Saleh, Dongmei Zuo, Hong Zhao, Marie-Christine Guiot, Ryan R Davis, Jeffrey P Gregg, Christopher Moraes, Anne-Claude Gingras, Morag Park
Triple-negative breast cancers (TNBCs) display a complex spectrum of mutations and chromosomal aberrations. Chromosome 5q (5q) loss is detected in up to 70% of TNBCs, but little is known regarding the genetic drivers associated with this event. Here, we show somatic deletion of a region syntenic with human 5q33.2-35.3 in a mouse model of TNBC. Mechanistically, we identify KIBRA as a major factor contributing to the effects of 5q loss on tumor growth and metastatic progression. Re-expression of KIBRA impairs metastasis in vivo and inhibits tumorsphere formation by TNBC cells in vitro...
March 20, 2018: Cell Reports
Abolfazl Namazi, Mohammad Forat-Yazdi, Mohammadali Jafari, Soudabeh Farahnak, Rezvan Nasiri, Elnaz Foroughi, Seyed Mojtaba Abolbaghaei, Hossein Neamatzadeh
BACKGROUND: The promoter -1082 A/G (rs1800896) polymorphism of Interleukin-10 (IL-10) gene have been widely reported and considered to have a significant role on gastric cancer risk, but the results are inconsistent. OBJECTIVE: To clarify the association, we conducted a meta-analysis to investigate the associations IL-10 -1082 A/G polymorphism with gastric cancer. METHODS: Eligible articles were identified by searching databases including PubMed, Web of Science, and Google Scholar up to August 03, 2017...
January 2018: Arquivos de Gastroenterologia
Daniela Hulcová, Kateřina Breiterová, Tomáš Siatka, Kamila Klímová, Lara Davani, Marcela Šafratová, Anna Hošťálková, Angela De Simone, Vincenza Andrisano, Lucie Cahlíková
Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine protein kinase that was originally identified as an enzyme involved in the control of glycogen metabolism. It plays a key role in diverse physiological processes including metabolism, the cell cycle, and gene expression by regulating a wide variety of well-known substances like glycogen synthase, tau-protein, and β-catenin. Recent studies have identified GSK-3β as a potential therapeutic target in Alzheimer´s disease, bipolar disorder, stroke, more than 15 types of cancer, and diabetes...
March 21, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Kathy H Y Shair, Akhil Reddy, Vaughn S Cooper
Latent membrane protein 1 (LMP1) is an Epstein-Barr virus (EBV) oncogenic protein that has no intrinsic enzymatic activity or sequence homology to cellular or viral proteins. The oncogenic potential of LMP1 has been ascribed to pleiotropic signaling properties initiated through protein-protein interactions in cytosolic membrane compartments, but the effects of LMP1 extend to nuclear and extracellular processes. Although LMP1 is one of the latent genes required for EBV-immortalization of B cells, the biology of LMP1 in the pathogenesis of the epithelial cancer nasopharyngeal carcinoma (NPC) is more complex...
March 21, 2018: Cancers
Xiao-Ming Wang, Yang Liu, Yu-Xia Fan, Zheng Liu, Qing-Ling Yuan, Meng Jia, Geng Zu-Shi, Ling Gu, Xiu-Bo Lu
Background LncRNA PTCSC3 is a tumor suppressor in thyroid cancer, and its role in drug resistance of anaplastic thyroid cancer (ATC) to chemotherapy drug doxorubicin was investigated in this study. Methods Expression of RNA and protein was analyzed by qRT-PCR and western blot, respectively. Flow cytometry was used to analyze the expression rate of CD133+ cells. The endogenous expression of related genes was modulated by recombinant plasmids and cell transfection. Combination condition and interaction between PTCSC3 and STAT3 were determined by RIP and RNA pull-down assay, respectively...
March 21, 2018: Cancer Biology & Therapy
Andrew VonHandorf, Francisco Javier Sánchez-Martín, Jacek Biesiada, Hongxia Zhang, Xiang Zhang, Mario Medvedovic, Alvaro Puga
Hexavalent chromium compounds are well-established respiratory carcinogens used in industrial processes. While inhalation exposure constitutes an occupational risk affecting mostly chromium workers, environmental exposure from drinking water is a widespread gastrointestinal cancer risk, affecting millions of people throughout the world. Cr(VI) is genotoxic, forming protein-Cr-DNA adducts and silencing tumor suppressor genes, but its mechanism of action at the molecular level is poorly understood. Our prior work using FAIRE showed that Cr(VI) disrupted the binding of transcription factors CTCF and AP-1 to their cognate chromatin sites...
March 21, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Dong-Min Kim, Dong Ho Kim, Woong Jung, Kye Young Lee, Dong-Eun Kim
Mutations in epidermal growth factor receptor (EGFR) are known as biomarkers that cause non-small cell lung cancer. Particularly, approximately 45% of non-small cell lung cancer patients possess a deletion in exon 19 of the EGFR gene. A less invasive method for detecting the EGFR mutation is required; thus, we developed a simple polymerase chain reaction (PCR)-based method for detecting EGFR exon 19 deletion by using a quencher-free fluorescent probe DNA and graphene oxide (GO). In the presence of the exon 19 deletion mutation, the fluorophore-labeled DNA probe was designed to be fully complementary to the mutant sequences...
March 21, 2018: Analyst
Nicolette Kapp, Xiao X Stander, Barend A Stander
This project investigated the in-vitro effects of a glycolytic inhibitor, 3-bromopyruvate (3-BrP), in combination with and a new in silico-designed inhibitor of the bromodomain-4 (BRD-4) protein, ITH-47, on the U937 acute myeloid leukemia cell line. 3-BrP is an agent that targets the altered metabolism of cancer cells by interfering with glucose metabolism in the glycolytic pathway. ITH-47 is an acetyl-lysine inhibitor that displaces bromdomain 4 proteins from chromatin by competitively binding to the acetyl-lysine recognition pocket of this bromodomain and extraterminal (BET) BRD protein, thereby preventing transcription of cancer-associated genes and further cell growth...
March 20, 2018: Anti-cancer Drugs
Nicola Silvestris, Oronzo Brunetti, Rosamaria Pinto, Daniela Petriella, Antonella Argentiero, Livia Fucci, Stefania Tommasi, Katia Danza, Simona De Summa
OBJECTIVES: Adenosquamous cancer of pancreas (ASCP) is a rare variant of pancreatic adenocarcinoma (PDAC). It is characterized by poor prognosis and lacks of literature data supporting the choice of systemic therapies. The role of immunotherapy for this malignancy is still unknown. In this study, we evaluated any differences between immune-related genes of PDAC and its adenosquamous variant with the aim to characterize these histothistotypes and eventually identify potential biomarkers useful for an immune-therapy approach in ASCP...
March 21, 2018: Expert Opinion on Therapeutic Targets
Saori Furuta, Gang Ren, Jian-Hua Mao, Mina J Bissell
How mammalian tissues maintain their architecture and tissue-specificity is poorly understood. Previously, we documented both the indispensable role of the extracellular matrix (ECM) protein, laminin-111 (LN1), in the formation of normal breast acini, and the phenotypic reversion of cancer cells to acini-like structures in 3-dimensional (3D) gels with inhibitors of oncogenic pathways. Here, we asked how laminin (LN) proteins integrate the signaling pathways necessary for morphogenesis. We report a surprising reciprocal circuitry comprising positive players: laminin-5 (LN5), nitric oxide (NO), p53, HOXD10 and three microRNAs (miRNAs) - that are involved in the formation of mammary acini in 3D...
March 21, 2018: ELife
Joana Torres, Remo Monti, Ariane L Moore, Makiko Seimiya, Yanrui Jiang, Niko Beerenwinkel, Christian Beisel, Jorge V Beira, Renato Paro
Tumor initiation is often linked to a loss of cellular identity. Transcriptional programs determining cellular identity are preserved by epigenetically-acting chromatin factors. Although such regulators are among the most frequently mutated genes in cancer, it is not well understood how an abnormal epigenetic condition contributes to tumor onset. In this work, we investigated the gene signature of tumors caused by disruption of the Drosophila epigenetic regulator, polyhomeotic (ph). In larval tissue ph mutant cells show a shift towards an embryonic-like signature...
March 21, 2018: ELife
Yourae Hong, Choa Park, Nayoung Kim, Juyeon Cho, Sung Ung Moon, Jongmin Kim, Euna Jeong, Sukjoon Yoon
BACKGROUND: Cell surface proteins have provided useful targets and biomarkers for advanced cancer therapies. The recent clinical success of antibody-drug conjugates (ADCs) highlights the importance of finding selective surface antigens for given cancer subtypes. We thus attempted to develop stand-alone software for the analysis of the cell surface transcriptome of patient cancer samples and to prioritize lineage- and/or mutation-specific over-expression markers in cancer cells. RESULTS: A total of 519 genes were selected as surface proteins, and their expression was profiled in 14 cancer subtypes using patient sample transcriptome data...
March 19, 2018: BMC Systems Biology
Sing-Han Huang, Yu-Shu Lo, Yong-Chun Luo, Yu-Yao Tseng, Jinn-Moon Yang
BACKGROUND: One of the crucial steps toward understanding the associations among molecular interactions, pathways, and diseases in a cell is to investigate detailed atomic protein-protein interactions (PPIs) in the structural interactome. Despite the availability of large-scale methods for analyzing PPI networks, these methods often focused on PPI networks using genome-scale data and/or known experimental PPIs. However, these methods are unable to provide structurally resolved interaction residues and their conservations in PPI networks...
March 19, 2018: BMC Systems Biology
Minji Jeon, Sunkyu Kim, Sungjoon Park, Heewon Lee, Jaewoo Kang
BACKGROUND: Drug combination therapy, which is considered as an alternative to single drug therapy, can potentially reduce resistance and toxicity, and have synergistic efficacy. As drug combination therapies are widely used in the clinic for hypertension, asthma, and AIDS, they have also been proposed for the treatment of cancer. However, it is difficult to select and experimentally evaluate effective combinations because not only is the number of cancer drug combinations extremely large but also the effectiveness of drug combinations varies depending on the genetic variation of cancer patients...
March 19, 2018: BMC Systems Biology
Yuet-Kin Leung, Bin Ouyang, Liang Niu, Changchun Xie, Jun Ying, Mario Medvedovic, Aimin Chen, Pal Weihe, Damaskini Valvi, Philippe Grandjean, Shuk-Mei Ho
Faroe islanders consume marine foods contaminated with methylmercury (MeHg), polychlorinated biphenyls (PCBs), and other toxicants associated with chronic disease risks. Differential DNA methylation at specific CpG sites in cord blood may serve as a surrogate biomarker of health impacts from chemical exposures. We aimed to identify key environmental chemicals in cord blood associated with DNA methylation changes in a population with elevated exposure to chemical mixtures. We studied 72 participants of a Faroese birth cohort recruited between 1986 and 1987 and followed until adulthood...
March 21, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Simin Mirakhor Samani, Tahmineh Ezazi Bojnordi, Manijeh Zarghampour, Sobhan Merat, Daniel F Fouladi
Our objective was to examine the expression rates of p53, Bcl-2 and Bax in endometrial carcinoma, endometrial hyperplasia and normal endometrium. A total of 94 endometrial frozen sections (carcinoma 48, hyperplasia 21, normal tissue 25) were examined immunohistochemically in terms of the expression rates of p53, Bcl-2 and Bax. All of the specimens in the non-malignant groups were positive for Bax, whereas this rate was 85.4% in the group with malignant specimens (p = .03). Conversely, p53 was expressed only in the cancerous group (77...
March 21, 2018: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
Sailendra Singh, Pallavi Pandey, Sumit Ghosh, Suchitra Banerjee
Andrographolide (AD) is the time-honoured pharmacologically active constituent of the traditionally renowned medicinal plant-Andrographis paniculata. Advancements in the target-oriented drug discovery process have further unravelled the immense therapeutic credibility of another unique molecule-neoandrographolide (NAD). The escalated market demand of these anti-cancer diterpenes is increasingly facing unrelenting hurdles of demand and supply disparity, attributable to their limited yield. Callus and adventitious root cultures were generated to explore their biosynthetic potentials which first time revealed NAD production along with AD...
March 20, 2018: Protoplasma
Hagit Schayek, Hila Korach, Yael Laitman, Rinat Bernstein-Molho, Eitan Friedman
PURPOSE: To define the mutational spectrum of several candidate gene mutations in Israeli male breast cancer cases. METHODS: MBC cases counselled at the Oncogenetics unit, Sheba Medical Center from January 1998 to June 2017 were included. Relevant clinical and oncological data and cancer phenotype were retrieved. All participants were genotyped for the predominant Jewish BRCA1 and BRCA2 germline mutations using a chip-based assay. Those who tested negative were further genotyped for three recurring mutations in CHEK2 (c...
March 21, 2018: Breast Cancer Research and Treatment
Ting-Ting Liu, Xi-Sheng Liu, Meng Zhang, Xue-Ni Liu, Fu-Xiang Zhu, Fang-Ming Zhu, Si-Wen Ouyang, Shan-Bao Li, Chen-Long Song, Hui-Min Sun, Su Lu, Yu Zhang, Jun Lin, Hua-Mei Tang, Zhi-Hai Peng
PURPOSE: Recent studies have determined that cartilage oligomeric matrix protein (COMP) plays a vital role in carcinogenesis. We sought to clarify the role of COMP in colon cancer. METHODS: We investigated gene expression data from The Cancer Genome Atlas (TCGA) dataset. Tissue microarrays (TMA) containing paired samples from 253 patients with colon cancer were subjected to immunostaining. COMP levels in serum of colon cancer patients and healthy donors were measured with ELISA...
March 20, 2018: Journal of Cancer Research and Clinical Oncology
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