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https://www.readbyqxmd.com/read/27935425/how-is-herstatin-a-tumour-suppressor-splice-variant-of-the-oncogene-her2-regulated
#1
Marco Silipo, Hannah Gautrey, Swapna Satam, Thomas Lennard, Alison Tyson-Capper
The human epidermal growth factor receptor 2 (HER2)/receptor tyrosine-protein kinasebB-2 (ERBB2) is over-expressed in 20-30% of breast tumours leading to faster growing and more aggressive tumours. Alternative splicing generates a functionally distinct HER2 variant called Herstatin, which is produced by the inclusion of intron 8. Herstatin acts as a tumour suppressor by effectively blocking HER2 activity and cell proliferation, while promoting apoptosis. In the present study we investigated HER2 pre-mRNA regulatory sequences and splicing factors which regulate the alternative splicing of Herstatin...
December 9, 2016: RNA Biology
https://www.readbyqxmd.com/read/27929754/hpv-16-e5-oncoprotein-is-expressed-in-early-stage-carcinogenesis-and-can-be-a-target-of-immunotherapy
#2
Paolini Francesca, Curzio Gianfranca, Marcelo Nazario Cordeiro, Silvia Massa, Luciano Mariani, Fulvia Pimpinelli, Antonio Carlos de Freitas, Rosella Franconi, Aldo Venuti
HPV16 persistent infection is a well-known condition that precedes human cancer development. High risk HPV E5 proteins cooperate with E6/E7 oncogenes to promote hyper-proliferation of infected cells leading to possible cancer progression. Thus, presence of E5 viral transcripts could be a key marker of active infection and, in turn, a target of immunotherapy. Purpose of the study is to detect E5 transcripts in clinical samples and to explore the activity of novel anti-HPV16 E5 DNA vaccines. HPV transcripts were detected by PCR with specific primers encompassing the splice-donor sites of E5 transcript...
December 8, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27929140/acfs-accurate-circrna-identification-and-quantification-from-rna-seq-data
#3
Xintian You, Tim Of Conrad
Circular RNAs (circRNAs) are a group of single-stranded RNAs in closed circular form. They are splicing-generated, widely expressed in various tissues and have functional implications in development and diseases. To facilitate genome-wide characterization of circRNAs using RNA-Seq data, we present a freely available software package named acfs. Acfs allows de novo, accurate and fast identification and abundance quantification of circRNAs from single- and paired-ended RNA-Seq data. On simulated datasets, acfs achieved the highest F1 accuracy and lowest false discovery rate among current state-of-the-art tools...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27926477/intra-or-extra-exosomal-secretion-of-hdgf-isoforms-the-extraordinary-function-of-the-hdgf-a-n-terminal-peptide
#4
Jessica Nüße, Eva-Maria Blumrich, Ursula Mirastschijski, Lennart Kappelmann, Sørge Kelm, Frank Dietz
Hepatoma-derived growth factor (HDGF) is a protein with diverse intracellular functions. Moreover, after non-conventional secretion, extracellular HDGF is able to influence different signalling pathways, leading for example to induction of processes like epithelialmesenchymal transition (EMT) and cell migration. Intriguingly, in recent proteome studies, HDGF was also found secreted by special microvesicles called exosomes. Recently, we demonstrated the existence of two new HDGF isoforms (B and C). These isoforms are involved in different cellular processes than HDGF-A...
December 7, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/27924559/isolation-and-characterization-of-intrinsically-active-mek-independent-mutants-of-mpk1-erk
#5
Tal Goshen-Lago, Dganit Melamed, Arie Admon, David Engelberg
The extracellular-regulated kinase (Erk) pathway is a major determinant in the control of diverse cellular processes, such as proliferation, differentiation, survival, and motility. The pathway executes its effects through kinases of the Erk family. Erks are not only critical for a variety of physiological processes, but are also associated with neurodegenerative diseases, cardiovascular diseases, diabetes and a large number of human cancers. However, the exact role of each Erk molecule in these biological and pathological processes is not fully determined...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27917920/transcriptome-and-long-noncoding-rna-sequencing-of-three-extracellular-vesicle-subtypes-released-from-the-human-colon-cancer-lim1863-cell-line
#6
Maoshan Chen, Rong Xu, Hong Ji, David W Greening, Alin Rai, Keiichi Izumikawa, Hideaki Ishikawa, Nobuhiro Takahashi, Richard J Simpson
Previously we reported that LIM1863 colorectal cancer (CRC) cells secrete three distinct extracellular vesicle subtypes - two subpopulations of exosomes (apical EpCAM-Exos and basolateral A33-Exos) and shed microvesicles (sMVs) - with distinct protein and miRNA signatures. Here, we extend our omics approach to understand the fundamental role of LIM1863-derived EVs by performing a comprehensive analysis of their mRNAs and long non-coding RNAs (lncRNAs) using RNA-Seq. We show that 2,389 mRNAs, 317 pseudogene transcripts, 1,028 lncRNAs and 206 short non-coding RNAs selectively distributed to (i...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27916892/molecular-mechanisms-of-p53-deregulation-in-cancer-an-overview-in-multiple-myeloma
#7
REVIEW
Ana B Herrero, Elizabeta A Rojas, Irena Misiewicz-Krzeminska, Patryk Krzeminski, Norma C Gutiérrez
The p53 pathway is inactivated in the majority of human cancers. Although this perturbation frequently occurs through the mutation or deletion of p53 itself, there are other mechanisms that can attenuate the pathway and contribute to tumorigenesis. For example, overexpression of important p53 negative regulators, such as murine double minute 2 (MDM2) or murine double minute 4 (MDM4), epigenetic deregulation, or even alterations in TP53 mRNA splicing. In this work, we will review the different mechanisms of p53 pathway inhibition in cancer with special focus on multiple myeloma (MM), the second most common hematological malignancy, with low incidence of p53 mutations/deletions but growing evidence of indirect p53 pathway deregulation...
November 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27916435/analytical-validation-of-androgen-receptor-splice-variant-7-detection-in-a-clinical-laboratory-improvement-amendments-clia-laboratory-setting
#8
Parvez M Lokhandwala, Stacy L Riel, Lisa Haley, Changxue Lu, Yan Chen, John Silberstein, Yezi Zhu, Gang Zheng, Ming-Tseh Lin, Christopher D Gocke, Alan W Partin, Emmanuel S Antonarakis, Jun Luo, James R Eshleman
Patients with castration-resistant prostate cancer (CRPC) often are treated with drugs that target the androgen receptor (AR) ligand-binding domain. Constitutively active AR splice variant 7 (AR-V7) lacks the ligand-binding domain and, if detected in circulating tumor cells, may be associated with resistance to these agents. We validated an AR-V7 assay in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. Circulating tumor cells were isolated, and mRNA was reverse-transcribed into cDNA...
December 1, 2016: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/27915475/how-precisely-can-prostate-cancer-be-managed
#9
REVIEW
Liyan Zhuang, Matthew T Johnson
Progress has been made in applying genetic information to disease management in the postgenomic era, and precision medicine is emerging in prostate cancer management. The prostate health index, the 4-kallikrein (4K) score, and the PCA3, TMPRSS2- ERG, and Prostarix tests have potential for refining prostate cancer screening in conjunction with traditional prostate-specific antigen testing. The Confirm MDx and PCA3 tests have shown promise in identifying men who need be rebiopsied after a primary negative biopsy...
November 2016: International Neurourology Journal
https://www.readbyqxmd.com/read/27913434/a-study-of-tp53-rna-splicing-illustrates-pitfalls-of-rna-seq-methodology
#10
Sunali Mehta, Peter Tsai, Annette Lasham, Hamish Campbell, Roger Reddel, Antony Braithwaite, Cristin Print
TP53 undergoes multiple RNA-splicing events, resulting in at least nine mRNA transcripts encoding at least 12 functionally different protein isoforms. Antibodies specific to p53 protein isoforms have proven difficult to develop, thus researchers must rely on the transcript information to infer isoform abundance. In this study, we used deep RNA-seq, droplet digital PCR (ddPCR), and real-time quantitative reverse transcriptase PCR (RT-qPCR) from nine human cell lines and RNA-seq data available for tumors in The Cancer Genome Atlas to analyze TP53 splice variant expression...
October 20, 2016: Cancer Research
https://www.readbyqxmd.com/read/27911856/splicing-factor-ratio-as-an-index-of-epithelial-mesenchymal-transition-and-tumor-aggressiveness-in-breast-cancer
#11
Pietro Fici, Giulia Gallerani, Anne-Pierre Morel, Laura Mercatali, Toni Ibrahim, Emanuela Scarpi, Dino Amadori, Alain Puisieux, Michel Rigaud, Francesco Fabbri
Epithelial-to-mesenchymal transition (EMT) has been shown to be associated with tumor progression and metastasis. During this process in breast cancer, a crucial role is played by alternative splicing systems. To identify a new early prognostic marker of metastasis, we evaluated EMT-related gene expression in breast cell lines, and in primary tumor tissue from 31 patients with early breast cancer, focusing our attention on EMT-related splicing factors ESRP1, ESRP2 and RBFOX2. Results showed that the expression patterns of these genes were indicative of the onset of EMT in in-vitro models, but not in tissue samples...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27907167/infusion-advancing-discovery-of-fusion-genes-and-chimeric-transcripts-from-deep-rna-sequencing-data
#12
Konstantin Okonechnikov, Aki Imai-Matsushima, Lukas Paul, Alexander Seitz, Thomas F Meyer, Fernando Garcia-Alcalde
Analysis of fusion transcripts has become increasingly important due to their link with cancer development. Since high-throughput sequencing approaches survey fusion events exhaustively, several computational methods for the detection of gene fusions from RNA-seq data have been developed. This kind of analysis, however, is complicated by native trans-splicing events, the splicing-induced complexity of the transcriptome and biases and artefacts introduced in experiments and data analysis. There are a number of tools available for the detection of fusions from RNA-seq data; however, certain differences in specificity and sensitivity between commonly used approaches have been found...
2016: PloS One
https://www.readbyqxmd.com/read/27903893/identification-of-a-novel-k311-ubiquitination-site-critical-for-androgen-receptor-transcriptional-activity
#13
Urszula L McClurg, David M W Cork, Steven Darby, Claudia A Ryan-Munden, Sirintra Nakjang, Leticia Mendes Côrtes, Achim Treumann, Luke Gaughan, Craig N Robson
The androgen receptor (AR) is the main driver of prostate cancer (PC) development and progression, and the primary therapeutic target in PC. To date, two functional ubiquitination sites have been identified on AR, both located in its C-terminal ligand binding domain (LBD). Recent reports highlight the emergence of AR splice variants lacking the LBD that can arise during disease progression and contribute to castrate resistance. Here, we report a novel N-terminal ubiquitination site at lysine 311. Ubiquitination of this site plays a role in AR stability and is critical for its transcriptional activity...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27902486/ed-b-fibronectin-expression-is-a-marker-of-epithelial-mesenchymal-transition-in-translational-oncology
#14
Iacopo Petrini, Serena Barachini, Vittoria Carnicelli, Sara Galimberti, Letizia Modeo, Roberto Boni, Martina Sollini, Paola Anna Erba
Fibronectin is a component of the extracellular matrix that links collagen fibers to integrins on the cell's surface. The splicing isoforms, containing the ED-B domain, are not expressed in adult tissues but only in tumor stroma or during embryonic development. Fibroblasts and endothelial cells express ED-B fibronectin during angiogenesis. Also cancer cells can synthetize ED-B fibronectin, but its function in tumor growth needs to be further elucidated.We evaluated the expression of ED-B fibronectin in prostate cancer cell lines: PC3 and DU145...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899618/rna-seq-mixology-designing-realistic-control-experiments-to-compare-protocols-and-analysis-methods
#15
Aliaksei Z Holik, Charity W Law, Ruijie Liu, Zeya Wang, Wenyi Wang, Jaeil Ahn, Marie-Liesse Asselin-Labat, Gordon K Smyth, Matthew E Ritchie
Carefully designed control experiments provide a gold standard for benchmarking different genomics research tools. A shortcoming of many gene expression control studies is that replication involves profiling the same reference RNA sample multiple times. This leads to low, pure technical noise that is atypical of regular studies. To achieve a more realistic noise structure, we generated a RNA-sequencing mixture experiment using two cell lines of the same cancer type. Variability was added by extracting RNA from independent cell cultures and degrading particular samples...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899596/chitars-3-1-the-enhanced-chimeric-transcripts-and-rna-seq-database-matched-with-protein-protein-interactions
#16
Alessandro Gorohovski, Somnath Tagore, Vikrant Palande, Assaf Malka, Dorith Raviv-Shay, Milana Frenkel-Morgenstern
Discovery of chimeric RNAs, which are produced by chromosomal translocations as well as the joining of exons from different genes by trans-splicing, has added a new level of complexity to our study and understanding of the transcriptome. The enhanced ChiTaRS-3.1 database (http://chitars.md.biu.ac.il) is designed to make widely accessible a wealth of mined data on chimeric RNAs, with easy-to-use analytical tools built-in. The database comprises 34 922: chimeric transcripts along with 11 714: cancer breakpoints...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899088/alternative-splicing-of-estrogen-receptor-alpha-in-hepatocellular-carcinoma
#17
Jian Zhang, Jianwei Ren, Jiamin Wei, Charing C N Chong, Dongjie Yang, Yulong He, George G Chen, Paul B S Lai
BACKGROUND: The role of estrogen receptor alpha (ERa), estrogen receptor beta (ERb) and ERa36 signaling in hepatocellular carcinoma (HCC) is not fully addressed. METHODS: In this study, three cohorts were included: (i) primary HCC patients (N = 76, cohort P), (ii) colorectal liver metastasis (mCRC) (N = 32, cohort S), and (iii) HCC from The Cancer Genome Atlas (TCGA) (N = 121). The levels of ERa36 and wtER36 were measured and their correlation with clinicopathologic features was determined...
November 30, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27895786/sprouty4-mrna-variants-and-protein-expressions-in-breast-and-lung-derived-cells
#18
Angelina Doriguzzi, Jihen Salhi, Hedwig Sutterlüty-Fall
Sprouty proteins are modulators of mitogen-induced signalling processes and are therefore hypothesized to affect malignant diseases. As a member of the Sprouty family, Sprouty4 has been previously shown to function as a tumour suppressor in lung and breast cancer. The present study analysed the expression of two known Sprouty4 splice variants in cells established from malignant and normal lung and breast tissues using semi-quantitative reverse transcription-polymerase chain reaction and immunoblotting. The results indicated that the expression of the two messenger RNA (mRNA) variants was reduced in the cells derived from malignant tissue in comparison to the normal counterparts...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27891760/muscle-ras-oncogene-homolog-mras-recurrent-mutation-in-borrmann-type-iv-gastric-cancer
#19
Makiko Yasumoto, Etsuko Sakamoto, Sachiko Ogasawara, Taro Isobe, Junya Kizaki, Akiko Sumi, Hironori Kusano, Jun Akiba, Takuji Torimura, Yoshito Akagi, Hiraku Itadani, Tsutomu Kobayashi, Shinichi Hasako, Masafumi Kumazaki, Shinji Mizuarai, Shinji Oie, Hirohisa Yano
The prognosis of patients with Borrmann type IV gastric cancer (Type IV) is extremely poor. Thus, there is an urgent need to elucidate the molecular mechanisms underlying the oncogenesis of Type IV and to identify new therapeutic targets. Although previous studies using whole-exome and whole-genome sequencing have elucidated genomic alterations in gastric cancer, none has focused on comprehensive genetic analysis of Type IV. To discover cancer-relevant genes in Type IV, we performed whole-exome sequencing and genome-wide copy number analysis on 13 patients with Type IV...
November 28, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27886673/in-silico-in-vitro-and-case-control-analyses-as-an-effective-combination-for-analyzing-brca1-and-brca2-unclassified-variants-in-a-population-based-sample
#20
Marta Rodríguez-Balada, Bàrbara Roig, Lourdes Martorell, Mireia Melé, Mònica Salvat, Elisabet Vilella, Joan Borràs, Josep Gumà
Ascertaining the clinical consequences of BRCA1 and BRCA2 variants of uncertain significance (VUS) is currently indispensable for providing effective genetic counseling and preventive actions for families with hereditary breast and ovarian cancer (HBOC). To this end, we conducted a combination of in silico prediction and cDNA splicing analyses of 13 BRCA1 and 10 BRCA2 VUS identified in our cohort as well as a case-control analysis in a population-based sample of 10 recurrent VUS. We observed consistent results between the in silico predictions and sequencing analyses for all analyzed VUS...
November 2016: Cancer Genetics
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