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https://www.readbyqxmd.com/read/29748619/eukaryotic-translation-initiation-factor-4-gamma-1-eif4g1-is-upregulated-during-prostate-cancer-progression-and-modulates-cell-growth-and-metastasis
#1
Praveen Kumar Jaiswal, Sweaty Koul, Prakash S T Shanmugam, Hari K Koul
eIF4G1, a critical component of the eIF4F complex, is required for cap-dependent mRNA translation, a process necessary for tumor growth and survival. However, the role of eIF4G1 has not been evaluated in Prostate Cancer (PCa). We observed an increased eIF4G1 protein levels in PCa tissues as compared to normal tissues. Analysis of the TCGA data revealed that eIF4G1 gene expression positively correlated with higher tumor grade and stage. Furthermore, eIF4G1 was over-expressed and or amplified, in 16% patients with metastatic PCa (SU2C/PCF Dream Team dataset) and in 59% of castration-resistant prostate cancer (CRPC) patients (Trento/Cornell/Broad dataset)...
May 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29744254/an-integrated-view-of-the-role-of-mir-130b-301b-mirna-cluster-in-prostate-cancer
#2
Rafael Sebastián Fort, Cecilia Mathó, Carolina Oliveira-Rizzo, Beatriz Garat, José Roberto Sotelo-Silveira, María Ana Duhagon
Prostate cancer is a major health problem worldwide due to its high incidence morbidity and mortality. There is currently a need of improved biomarkers, capable to distinguish mild versus aggressive forms of the disease, and thus guide therapeutic decisions. Although miRNAs deregulated in cancer represent exciting candidates as biomarkers, its scientific literature is frequently fragmented in dispersed studies. This problem is aggravated for miRNAs belonging to miRNA gene clusters with shared target genes. The miRNA cluster composed by hsa-mir-130b and hsa-mir-301b precursors was recently involved in prostate cancer pathogenesis, yet different studies assigned it opposite effects on the disease...
2018: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29739972/cell-type-specific-expression-of-oncogenic-and-tumor-suppressive-micrornas-in-the-human-prostate-and-prostate-cancer
#3
Binod Kumar, Avi Z Rosenberg, Su Mi Choi, Karen Fox-Talbot, Angelo M De Marzo, Larisa Nonn, W Nathaniel Brennen, Luigi Marchionni, Marc K Halushka, Shawn E Lupold
MiR-1 and miR-143 are frequently reduced in human prostate cancer (PCa), while miR-141 and miR-21 are frequently elevated. Consequently, these miRNAs have been studied as cell-autonomous tumor suppressors and oncogenes. However, the cell-type specificity of these miRNAs is not well defined in prostate tissue. Through two different microdissection techniques, and droplet digital RT-PCR, we quantified these miRNAs in the stroma and epithelium of radical prostatectomy specimens. In contrast to their purported roles as cell-autonomous tumor suppressors, we found miR-1 and miR-143 expression to be predominantly stromal...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29725504/robust-genomic-copy-number-predictor-of-pan-cancer-metastasis
#4
Alexander Pearlman, Kinnari Upadhyay, Kim Cole, John Loke, Katherine Sun, Susan Fineberg, Stephen J Freedland, Yongzhao Shao, Harry Ostrer
Copy number alterations(CNAs) are the most common genetic changes observed in many cancers, reflecting the innate chromosomal instability of this disorder. Yet, how these alterations affect gene function to promote metastases across different tumor types has not been established. In this study, we developed a pan-cancer metastasis potential score (panMPS) based on observed CNAs. panMPS predicts metastasis and metastasis-free survival in cohorts of patients with prostate cancer, triple negative breast cancer and lung adenocarcinoma, and overall survival in the Metabric breast cancer cohort and three cohorts from The Cancer Genome Atlas (TCGA), including prostate, breast and lung adenocarcinoma...
January 2018: Genes & Cancer
https://www.readbyqxmd.com/read/29685789/integrative-epi-genomic-analysis-to-predict-response-to-androgen-deprivation-therapy-in-prostate-cancer
#5
Sukanya Panja, Sheida Hayati, Nusrat J Epsi, James Scott Parrott, Antonina Mitrofanova
Therapeutic resistance is a central problem in clinical oncology. We have developed a systematic genome-wide computational methodology to allow prioritization of patients with favorable and poor therapeutic response. Our method, which integrates DNA methylation and mRNA expression data, uncovered a panel of 5 differentially methylated sites, which explain expression changes in their site-harboring genes, and demonstrated their ability to predict primary resistance to androgen-deprivation therapy (ADT) in the TCGA prostate cancer patient cohort (hazard ratio = 4...
April 12, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29673323/indel-detection-from-dna-and-rna-sequencing-data-with-transindel
#6
Rendong Yang, Jamie L Van Etten, Scott M Dehm
BACKGROUND: Insertions and deletions (indels) are a major class of genomic variation associated with human disease. Indels are primarily detected from DNA sequencing (DNA-seq) data but their transcriptional consequences remain unexplored due to challenges in discriminating medium-sized and large indels from splicing events in RNA-seq data. RESULTS: Here, we developed transIndel, a splice-aware algorithm that parses the chimeric alignments predicted by a short read aligner and reconstructs the mid-sized insertions and large deletions based on the linear alignments of split reads from DNA-seq or RNA-seq data...
April 19, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29662167/sequencing-of-prostate-cancers-identifies-new-cancer-genes-routes-of-progression-and-drug-targets
#7
David C Wedge, Gunes Gundem, Thomas Mitchell, Dan J Woodcock, Inigo Martincorena, Mohammed Ghori, Jorge Zamora, Adam Butler, Hayley Whitaker, Zsofia Kote-Jarai, Ludmil B Alexandrov, Peter Van Loo, Charlie E Massie, Stefan Dentro, Anne Y Warren, Clare Verrill, Dan M Berney, Nening Dennis, Sue Merson, Steve Hawkins, William Howat, Yong-Jie Lu, Adam Lambert, Jonathan Kay, Barbara Kremeyer, Katalin Karaszi, Hayley Luxton, Niedzica Camacho, Luke Marsden, Sandra Edwards, Lucy Matthews, Valeria Bo, Daniel Leongamornlert, Stuart McLaren, Anthony Ng, Yongwei Yu, Hongwei Zhang, Tokhir Dadaev, Sarah Thomas, Douglas F Easton, Mahbubl Ahmed, Elizabeth Bancroft, Cyril Fisher, Naomi Livni, David Nicol, Simon Tavaré, Pelvender Gill, Christopher Greenman, Vincent Khoo, Nicholas Van As, Pardeep Kumar, Christopher Ogden, Declan Cahill, Alan Thompson, Erik Mayer, Edward Rowe, Tim Dudderidge, Vincent Gnanapragasam, Nimish C Shah, Keiran Raine, David Jones, Andrew Menzies, Lucy Stebbings, Jon Teague, Steven Hazell, Cathy Corbishley, Johann de Bono, Gerhardt Attard, William Isaacs, Tapio Visakorpi, Michael Fraser, Paul C Boutros, Robert G Bristow, Paul Workman, Chris Sander, Freddie C Hamdy, Andrew Futreal, Ultan McDermott, Bissan Al-Lazikani, Andrew G Lynch, G Steven Bova, Christopher S Foster, Daniel S Brewer, David E Neal, Colin S Cooper, Rosalind A Eeles
Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers...
April 16, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29599847/a-multiplatform-approach-identifies-mir-152-3p-as-a-common-epigenetically-regulated-onco-suppressor-in-prostate-cancer-targeting-tmem97
#8
João Ramalho-Carvalho, Céline S Gonçalves, Inês Graça, David Bidarra, Eva Pereira-Silva, Sofia Salta, Maria Inês Godinho, Antonio Gomez, Manel Esteller, Bruno M Costa, Rui Henrique, Carmen Jerónimo
Background: Prostate cancer (PCa) is a major cause of morbidity and mortality in men worldwide. MicroRNAs are globally downregulated in PCa, especially in poorly differentiated tumors. Nonetheless, the underlying mechanisms are still elusive. Herein, using combined analysis of microRNAs expression and genomewide DNA methylation, we aimed to identify epigenetically downregulated microRNAs in PCa. Results: We found that miR-152-3p was underexpressed in PCa and that lower expression levels were associated with promoter hypermethylation in accordance with TCGA dataset analysis...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29593348/profiles-of-mirna-isoforms-and-trna-fragments-in-prostate-cancer
#9
Rogan G Magee, Aristeidis G Telonis, Phillipe Loher, Eric Londin, Isidore Rigoutsos
MicroRNA (miRNA) isoforms ("isomiRs") and tRNA-derived fragments ("tRFs") are powerful regulatory non-coding RNAs (ncRNAs). In human tissues, both types of molecules are abundant, with expression patterns that depend on a person's race, sex and population origin. Here, we present our analyses of the Prostate Cancer (PRAD) datasets of The Cancer Genome Atlas (TCGA) from the standpoint of isomiRs and tRFs. This study represents the first simultaneous examination of isomiRs and tRFs in a large cohort of PRAD patients...
March 28, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29587239/enhanced-expression-of-srpk2-contributes-to-aggressive-progression-and-metastasis-in-prostate-cancer
#10
Yang Jia Zhuo, Ze Zhen Liu, Song Wan, Zhi Duan Cai, Jian Jiang Xie, Zhou da Cai, Sheng da Song, Yue Ping Wan, Wei Hua, Wei de Zhong, Chin Lee Wu
Serine/Arginine-Rich Protein-Specific Kinase-2 (SRSF protein kinase-2, SRPK2) is up-regulated in multiple human tumors. However, the expression, function and clinical significance of SRPK2 in prostate cancer (PCa) has not yet been understood. We therefore aimed to determine the association of SRPK2 with tumor progression and metastasis in PCa patients in our present study. The expression of SRPK2 was detected by some public datasets and validated using a clinical tissue microarray (TMA) by immunohistochemistry...
March 24, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29581838/high-expression-of-slco2b1-is-associated-with-prostate-cancer-recurrence-after-radical-prostatectomy
#11
Tomoaki Terakawa, Eriko Katsuta, Li Yan, Nitesh Turaga, Kerry-Ann McDonald, Masato Fujisawa, Khurshid A Guru, Kazuaki Takabe
Solute carrier organic anion (SLCO) gene families encode organic anion transport proteins, which are transporters that up-take a number of substrates including androgens. Among them, high expression of SLCO2B1 is known to associate with the resistance to androgen deprivation therapy in prostate cancer (PCa). We hypothesized that high expression of SLCO genes enhances PCa progression by promoting the influx of androgen. Here, we demonstrated the impact of the expression levels of SLCO2B1 on prognosis in localized PCa after radical prostatectomy (RP) utilizing 494 PCa cases in The Cancer Genome Atlas (TCGA)...
March 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29568403/exosomal-microrna-profiling-to-identify-hypoxia-related-biomarkers-in-prostate-cancer
#12
Gati K Panigrahi, Anand Ramteke, Diane Birks, Hamdy E Abouzeid Ali, Sujatha Venkataraman, Chapla Agarwal, Rajeev Vibhakar, Lance D Miller, Rajesh Agarwal, Zakaria Y Abd Elmageed, Gagan Deep
Hypoxia and expression of hypoxia-related biomarkers are associated with disease progression and treatment failure in prostate cancer (PCa). We have reported that exosomes (nanovesicles of 30-150 nm in diameter) secreted by human PCa cells under hypoxia promote invasiveness and stemness in naïve PCa cells. Here, we identified the unique microRNAs (miRNAs) loaded in exosomes secreted by PCa cells under hypoxia. Using TaqMan® array microRNA cards, we analyzed the miRNA profile in exosomes secreted by human PCa LNCaP cells under hypoxic (ExoHypoxic ) and normoxic (ExoNormoxic ) conditions...
March 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29559248/role-of-mir-452-5p-in-the-tumorigenesis-of-prostate-cancer-a-study-based-on-the-cancer-genome-atl-tcga-gene-expression-omnibus-geo-and-bioinformatics-analysis
#13
Li Gao, Li-Jie Zhang, Sheng-Hua Li, Li-Li Wei, Bin Luo, Rong-Quan He, Shuang Xia
BACKGROUND: MiR-452-5p has been reported to be down-regulated in prostate cancer, affecting the development of this type of cancer. However, the molecular mechanism of miR-452-5p in prostate cancer remains unclear. Therefore, we investigated the network of target genes of miR-452-5p in prostate cancer using bioinformatics analyses. MATERIALS AND METHODS: We first analyzed the expression profiles and prognostic value of miR-452-5p in prostate cancer tissues from a public database...
March 6, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29529299/the-association-between-copy-number-aberration-dna-methylation-and-gene-expression-in-tumor-samples
#14
Wei Sun, Paul Bunn, Chong Jin, Paul Little, Vasyl Zhabotynsky, Charles M Perou, David Neil Hayes, Mengjie Chen, Dan-Yu Lin
We systematically studied the association between somatic copy number aberration (SCNA), DNA methylation and gene expression using -omic data from The Cancer Genome Atlas (TCGA) on six cancer types: breast cancer, colon cancer, glioblastoma, leukemia, lower-grade glioma and prostate cancer. A major challenge for such integrated study is that the association between DNA methylation and gene expression is severely confounded by tumor purity and cell type composition, which are often unobserved and difficult to estimate...
April 6, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29515971/the-expression-and-prognostic-impact-of-immune-cytolytic-activity-related-markers-in-human-malignancies-a-comprehensive-meta-analysis
#15
Constantinos Roufas, Dimitrios Chasiotis, Anestis Makris, Christodoulos Efstathiades, Christos Dimopoulos, Apostolos Zaravinos
Background: Recently, immune-checkpoint blockade has shown striking clinical results in different cancer patients. However, a significant inter-individual and inter-tumor variability exists among different cancers. The expression of the toxins granzyme A (GZMA) and perforin 1 (PRF1), secreted by effector cytotoxic T cells and natural killer (NK) cells, were recently used as a denominator of the intratumoral immune cytolytic activity (CYT). These levels are significantly elevated upon CD8+ T-cell activation as well as during a productive clinical response against immune-checkpoint blockade therapies...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29455299/prostate-specific-membrane-antigen-in-breast-cancer-a-comprehensive-evaluation-of-expression-and-a-case-report-of-radionuclide-therapy
#16
Yuri Tolkach, Heidrun Gevensleben, Ralph Bundschuh, Aydan Koyun, Daniela Huber, Christina Kehrer, Thomas Hecking, Mignon-Denise Keyver-Paik, Christina Kaiser, Hojjat Ahmadzadehfar, Markus Essler, Walther Kuhn, Glen Kristiansen
PURPOSE: Prostate-specific membrane antigen (PSMA), a protein product of the folate hydrolase 1 (FOLH1) gene, is gaining increasing acceptance as a target for positron emission tomography/computer tomography (PET/CT) imaging in patients with several cancer types, including breast cancer. So far, PSMA expression in breast cancer endothelia has not been sufficiently characterized. METHODS: This study comprised 315 cases of invasive carcinoma of no special type (NST) and lobular breast cancer (median follow-up time 9...
February 17, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29445424/promoter-methylation-of-dna-damage-repair-ddr-genes-in-human-tumor-entities-rbbp8-ctip-is-almost-exclusively-methylated-in-bladder-cancer
#17
Jolein Mijnes, Jürgen Veeck, Nadine T Gaisa, Eduard Burghardt, Tim C de Ruijter, Sonja Gostek, Edgar Dahl, David Pfister, Sebastian C Schmid, Ruth Knüchel, Michael Rose
Background: Genome-wide studies identified pan-cancer genes and shared biological networks affected by epigenetic dysregulation among diverse tumor entities. Here, we systematically screened for hypermethylation of DNA damage repair (DDR) genes in a comprehensive candidate-approach and exemplarily identify and validate candidate DDR genes as targets of epigenetic inactivation unique to bladder cancer (BLCA), which may serve as non-invasive biomarkers. Methods: Genome-wide DNA methylation datasets (2755 CpG probes of n  = 7819 tumor and n  = 659 normal samples) of the TCGA network covering 32 tumor entities were analyzed in silico for 177 DDR genes...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29394925/nc886-is-epigenetically-repressed-in-prostate-cancer-and-acts-as-a-tumor-suppressor-through-the-inhibition-of-cell-growth
#18
Rafael Sebastián Fort, Cecilia Mathó, Murilo Vieira Geraldo, María Carolina Ottati, Alex Shimura Yamashita, Kelly Cristina Saito, Katia Ramos Moreira Leite, Manuel Méndez, Noemí Maedo, Laura Méndez, Beatriz Garat, Edna Teruko Kimura, José Roberto Sotelo-Silveira, María Ana Duhagon
BACKGROUND: Nc886 is a 102 bp non-coding RNA transcript initially classified as a microRNA precursor (Pre-miR-886), later as a divergent homologue of the vault RNAs (vtRNA 2-1) and more recently as a novel type of RNA (nc886). Although nc886/vtRNA2-1/Pre-miR-886 identity is still controversial, it was shown to be epigenetically controlled, presenting both tumor suppressor and oncogenic function in different cancers. Here, we study for the first time the role of nc886 in prostate cancer...
February 2, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29389061/the-mir-203-snai2-axis-regulates-prostate-tumor-growth-migration-angiogenesis-and-stemness-potentially-by-modulating-gsk-3%C3%AE-%C3%AE-catenin-signal-pathway
#19
Xinxin Tian, Fangfang Tao, Baotong Zhang, Jin-Tang Dong, Zhiqian Zhang
Dysregulation of microRNA expression plays a pivotal role in the initiation and progression of a variety of human carcinomas including prostate cancer. Our previous studies have demonstrated that the silence of miR-203 contributes to the invasiveness of malignant breast cancer cells by targeting SNAI2. However, the effects and underlying mechanisms of miR-203/SNAI2 axis in prostate cancer have not been elucidated. The aim of this study is to explore the effects of miR-203/SNAI2 axis on the biological characteristics of prostate carcinomas both in vitro and in vivo...
March 2018: IUBMB Life
https://www.readbyqxmd.com/read/29367276/regulation-of-udp-glucuronosyltransferase-2b15-by-mir-331-5p-in-prostate-cancer-cells-involves-canonical-and-non-canonical-target-sites
#20
Dhilushi Wijayakumara, Peter Ian Mackenzie, Ross A McKinnon, Dong Gui Hu, Robyn Meech
UGT2B15 is an important androgen metabolizing UGT and the mechanisms controlling its expression are of considerable interest. Recent studies showed that miR-376c regulates UGT2B15 in prostate cancer cells via a canonical target site in the 3'untranslated region (3'UTR). The UGT2B15 3'UTR also contains a canonical miR-331-5p target site; previous work indicated that deleting this site reduced, but did not abolish, the ability of miR-331-5p to repress a luciferase reporter carrying the UGT2B15 3'UTR. We report here the discovery and characterization of a second, non-canonical miR-331-5p target site in the UGT2B15 3'UTR...
January 24, 2018: Journal of Pharmacology and Experimental Therapeutics
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