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https://www.readbyqxmd.com/read/28818525/whole-transcriptome-microarray-analysis-reveals-regulation-of-rab4-by-rbm5-in-neurons
#1
Travis C Jackson, Shawn E Kotermanski, Patrick M Kochanek
RNA binding motif 5 (RBM5) is a nuclear protein that modulates gene transcription and mRNA splicing in cancer cells. The brain is among the highest RBM5 expressing organ in the body but its mRNA target(s) or functions in the CNS have not been elucidated. Here we knocked down (KO) RBM5 in primary rat cortical neurons and analyzed total RNA extracts by gene microarray vs. neurons transduced with lentivirus to deliver control (non-targeting) shRNA. The mRNA levels of Sec23A (involved in ER-Golgi transport) and the small GTPase Rab4a (involved in endocytosis/protein trafficking) were increased in RBM5 KO neurons relative to controls...
August 14, 2017: Neuroscience
https://www.readbyqxmd.com/read/28818355/ar-v7-in-peripheral-whole-blood-of-patients-with-castration-resistant-prostate-cancer-association-with-treatment-specific-outcome-under-abiraterone-and-enzalutamide
#2
Anna Katharina Seitz, Silvia Thoene, Andreas Bietenbeck, Roman Nawroth, Robert Tauber, Mark Thalgott, Sebastian Schmid, Ramona Secci, Margitta Retz, Jürgen E Gschwend, Jürgen Ruland, Christof Winter, Matthias M Heck
BACKGROUND: It has been demonstrated that androgen receptor splice variant 7 (AR-V7) expression in circulating tumor cells (CTCs) predicts poor treatment response in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone or enzalutamide. OBJECTIVE: To develop a practical and robust liquid profiling approach for direct quantification of AR-V7 in peripheral whole blood without the need for CTC capture and to determine its potential for predicting treatment response in mCRPC patients...
August 14, 2017: European Urology
https://www.readbyqxmd.com/read/28815885/novel-landscape-of-hla-g-isoforms-expressed-in-clear-cell-renal-cell-carcinoma-patients
#3
Diana Tronik-Le Roux, Julie Renard, Jérôme Vérine, Victor Renault, Emmanuel Tubacher, Joel LeMaoult, Nathalie Rouas-Freiss, Jean-François Deleuze, François Desgrandschamps, Edgardo D Carosella
Immune-checkpoints are powerful inhibitory molecules that promote tumor survival. Their blockade is now recognized as providing effective therapeutic benefit against cancer. HLA-G, a recently identified immune checkpoint, has been detected in many types of primary tumors and metastases, in malignant effusions as well as on tumor-infiltrating cells, particularly in patients with clear cell renal cell carcinoma (ccRCC). Here, in order to define a possible anti-cancer therapy, we used a molecular approach based on an unbiased strategy that combines transcriptome determination and immunohistochemical labeling, to analyze in-depth, the HLA-G isoforms expressed in these tumors...
August 16, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28811661/myst2-kat7-histone-acetyltransferase-interaction-proteomics-reveals-tumour-suppressor-niam-as-a-novel-binding-partner-in-embryonic-stem-cells
#4
Mercedes Pardo, Lu Yu, Shihpei Shen, Peri Tate, Daniel Bode, Blake L Letney, Dawn E Quelle, William Skarnes, Jyoti S Choudhary
MYST histone acetyltransferases have crucial functions in transcription, replication and DNA repair and are hence implicated in development and cancer. Here we characterise Myst2/Kat7/Hbo1 protein interactions in mouse embryonic stem cells by affinity purification coupled to mass spectrometry. This study confirms that in embryonic stem cells Myst2 is part of H3 and H4 histone acetylation complexes similar to those described in somatic cells. We identify a novel Myst2-associated protein, the tumour suppressor protein Niam (Nuclear Interactor of ARF and Mdm2)...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811363/targeting-ar-variant-coactivator-interactions-to-exploit-prostate-cancer-vulnerabilities
#5
Fiorella Magani, Stephanie O Peacock, Meghan A Rice, Maria J Martinez, Ann M Greene, Pablo S Magani, Rolando Lyles, Jonathan R Weitz, Kerry L Burnstein
Castration-resistant prostate cancer (CRPC) progresses rapidly and is incurable. Constitutively active androgen receptor splice variants (AR-Vs) represent a well-established mechanism of therapeutic resistance and disease progression. These variants lack the AR ligand-binding domain and, as such, are not inhibited by androgen deprivation therapy (ADT), which is the standard systemic approach for advanced PC. Signaling by AR-Vs, including the clinically relevant AR-V7, is augmented by Vav3, an established AR coactivator in CRPC...
August 15, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28811331/targeting-a-single-alternative-polyadenylation-site-coordinately-blocks-expression-of-androgen-receptor-mrna-splice-variants-in-prostate%C3%A2-cancer
#6
Jamie L Van Etten, Michael Nyquist, Yingming Li, Rendong Yang, Yeung Ho, Rachel M Johnson, Olivia Ondigi, Daniel F Voytas, Christine Henzler, Scott M Dehm
Prostate cancer is the second leading cause of male cancer deaths due to disease progression to castration resistant prostate cancer (CRPC). Androgen receptor (AR) splice variants including AR-V7 function as constitutively active transcription factors in CRPC cells, thereby promoting resistance to AR-targeted therapies. To date, there are no AR variant specific treatments for CRPC. Here we report that the splicing of AR variants AR-V7 as well as AR-V1 and AR-V9 is regulated coordinately by a single polyadenylation signal in AR intron 3...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28810637/binding-of-line-1-rna-to-psf-transcriptionally-promotes-gage6-and-regulates-cell-proliferation-and-tumor-formation-in-vitro
#7
Jiao Lv, Ziyi Zhao
Hepatocellular carcinoma (HCC) has one of the highest mortality rates among numerous types of cancer. It has been demonstrated that in hepatitis B (HBV)-associated HCC, the expression of chimeric fusion transcript HBx-long interspersed nuclear element-1 (LINE-1) initiated by HBV integration is correlated with hepatocarcinogenesis and poor patient survival rates. Furthermore, increased rates of LINE-1 hypomethylation have been detected in HCC tissues compared with adjacent tissues. This suggests that individual LINE-1 RNA (L1 RNA) serves an important role in the processes of hepatocarcinogenesis...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28806747/low-lamin-a-expression-in-lung-adenocarcinoma-cells-from-pleural-effusions-is-a-pejorative-factor-associated-with-high-number-of-metastatic-sites-and-poor-performance-status
#8
Elise Kaspi, Diane Frankel, Julien Guinde, Sophie Perrin, Sophie Laroumagne, Andrée Robaglia-Schlupp, Kevin Ostacolo, Karim Harhouri, Rachid Tazi-Mezalek, Joelle Micallef, Hervé Dutau, Pascale Tomasini, Annachiara De Sandre-Giovannoli, Nicolas Lévy, Pierre Cau, Philippe Astoul, Patrice Roll
The type V intermediate filament lamins are the principal components of the nuclear matrix, including the nuclear lamina. Lamins are divided into A-type and B-type, which are encoded by three genes, LMNA, LMNB1, and LMNB2. The alternative splicing of LMNA produces two major A-type lamins, lamin A and lamin C. Previous studies have suggested that lamins are involved in cancer development and progression. A-type lamins have been proposed as biomarkers for cancer diagnosis, prognosis, and/or follow-up. The aim of the present study was to investigate lamins in cancer cells from metastatic pleural effusions using immunofluorescence, western blotting, and flow cytometry...
2017: PloS One
https://www.readbyqxmd.com/read/28802831/validation-of-a-targeted-rna-sequencing-assay-for-kinase-fusion-detection-in-solid-tumors
#9
Julie W Reeser, Dorrelyn Martin, Jharna Miya, Esko A Kautto, Ezra Lyon, Eliot Zhu, Michele R Wing, Amy Smith, Matthew Reeder, Eric Samorodnitsky, Hannah Parks, Karan R Naik, Joseph Gozgit, Nicholas Nowacki, Kurtis D Davies, Marileila Varella-Garcia, Lianbo Yu, Aharon G Freud, Joshua Coleman, Dara L Aisner, Sameek Roychowdhury
Kinase gene fusions are important drivers of oncogenic transformation and can be inhibited with targeted therapies. Clinical grade diagnostics using RNA sequencing to detect gene rearrangements in solid tumors are limited, and the few that are available require prior knowledge of fusion break points. To address this, we have analytically validated a targeted RNA sequencing assay (OSU-SpARKFuse) for fusion detection that interrogates complete transcripts from 93 kinase and transcription factor genes. From a total of 74 positive and 36 negative control samples, OSU-SpARKFuse had 93...
August 8, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28801664/stat3-induced-long-noncoding-rnas-in-multiple-myeloma-cells-display-different-properties-in-cancer
#10
Stefanie Binder, Nadine Hösler, Diana Riedel, Ivonne Zipfel, Tilo Buschmann, Christoph Kämpf, Kristin Reiche, Renate Burger, Martin Gramatzki, Jörg Hackermüller, Peter F Stadler, Friedemann Horn
Interleukin-6 (IL-6)-activated Signal Transducer and Activator of Transcription 3 (STAT3) facilitates survival in the multiple myeloma cell line INA-6 and therefore represents an oncogenic key player. However, the biological mechanisms are still not fully understood. In previous studies we identified microRNA-21 as a STAT3 target gene with strong anti-apoptotic potential, suggesting that noncoding RNAs have an impact on the pathogenesis of human multiple myeloma. Here, we describe five long noncoding RNAs (lncRNAs) induced by IL-6-activated STAT3, which we named STAiRs...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28796317/mutation-status-of-rad51c-palb2-and-brip1-in-100-japanese-familial-breast-cancer-cases-without-brca1-and-brca2-mutations
#11
Katsutoshi Sato, Mio Koyasu, Sachio Nomura, Yuri Sato, Mizuho Kita, Yuumi Ashihara, Yasue Adachi, Shinji Ohno, Takuji Iwase, Dai Kitagawa, Eri Nakashima, Reiko Yoshida, Yoshio Miki, Masami Arai
In addition to BRCA1 and BRCA2, RAD51C, PALB2, and BRIP1 are known as breast cancer susceptibility genes. However, the mutation status of these genes in Japanese familial breast cancer cases has not been evaluated yet. To this end, we analyzed the exon sequence and genomic rearrangement of RAD51C, PALB2, and BRIP1 in 100 Japanese patients diagnosed with familial breast and ovarian cancer and without BRCA1 and BRCA2 mutations. We detected a large deletion from exon 6 to 9 in RAD51C, 4 novel BRIP1 missense variants containing 3 novel non-synonymous variants, c...
August 10, 2017: Cancer Science
https://www.readbyqxmd.com/read/28791797/emerging-roles-of-hnrnpa1-in-modulating-malignant-transformation
#12
REVIEW
Rajat Roy, Yueyang Huang, Michael J Seckl, Olivier E Pardo
Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA-binding proteins associated with complex and diverse biological processes such as processing of heterogeneous nuclear RNAs (hnRNAs) into mature mRNAs, RNA splicing, transactivation of gene expression, and modulation of protein translation. hnRNPA1 is the most abundant and ubiquitously expressed member of this protein family and has been shown to be involved in multiple molecular events driving malignant transformation. In addition to selective mRNA splicing events promoting expression of specific protein variants, hnRNPA1 regulates the gene expression and translation of several key players associated with tumorigenesis and cancer progression...
August 8, 2017: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/28789987/regulation-of-splicing-and-circularisation-of-rna-in-epithelial-mesenchymal-plasticity
#13
REVIEW
Daniel P Neumann, Gregory J Goodall, Philip A Gregory
Interconversions between epithelial and mesenchymal states, often referred to as epithelial mesenchymal transition (EMT) and its reverse MET, play important roles in embryonic development and are recapitulated in various adult pathologies including cancer progression. These conversions are regulated by complex transcriptional and post-transcriptional mechanisms including programs of alternative splicing which are orchestrated by specific splicing factors. This review will focus on the latest developments in our understanding of the splicing factors regulating epithelial mesenchymal plasticity associated with cancer progression and the induction of pluripotency, including potential roles for circular RNAs (circRNAs) which have been recently implicated in these processes...
August 5, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28783698/maintenance-of-macrophage-transcriptional-programs-and-intestinal-homeostasis-by-epigenetic-reader-sp140
#14
Stuti Mehta, D Alexander Cronkite, Megha Basavappa, Tahnee L Saunders, Fatemeh Adiliaghdam, Hajera Amatullah, Sara A Morrison, Jose D Pagan, Robert M Anthony, Pierre Tonnerre, Georg M Lauer, James C Lee, Sreehaas Digumarthi, Lorena Pantano, Shannan J Ho Sui, Fei Ji, Ruslan Sadreyev, Chan Zhou, Alan C Mullen, Vinod Kumar, Yang Li, Cisca Wijmenga, Ramnik J Xavier, Terry K Means, Kate L Jeffrey
Epigenetic "readers" that recognize defined posttranslational modifications on histones have become desirable therapeutic targets for cancer and inflammation. SP140 is one such bromodomain- and plant homeodomain (PHD)-containing reader with immune-restricted expression, and single-nucleotide polymorphisms (SNPs) within SP140 associate with Crohn's disease (CD). However, the function of SP140 and the consequences of disease-associated SP140 SNPs have remained unclear. We show that SP140 is critical for transcriptional programs that uphold the macrophage state...
March 3, 2017: Science Immunology
https://www.readbyqxmd.com/read/28781253/-omics-technologies-in-diagnostics-of-lung-adenocarcinoma
#15
REVIEW
S E Novikova, L K Kurbatov, M G Zavialova, V G Zgoda, A I Archakov
To date lung adenocarcinoma (LAC) is the most common type of lung cancer. Numerous studies on LAC biology resulted in identification of crucial mutations in protooncogenes and activating neoplastic transformation pathways. Therapeutic approaches that significantly increase the survival rate of patients with LAC of different etiology have been developed and introduced into clinical practice. However, the main problem in the treatment of LAC is early diagnosis, taking into account both factors and mechanisms responsible in tumor initiation and progression...
May 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28776911/long-non-coding-rnas-as-an-epigenetic-regulator-in-human-cancers
#16
REVIEW
Yutaka Kondo, Keiko Shinjo, Keisuke Katsushima
Recent studies have demonstrated the important multiple roles of long non-coding RNAs (lncRNAs) during oncogenic transformation. Because the coding genome accounts for a small amount of total DNA, and many mutations leading to cancer occur in the non-coding genome, it is plausible that the dysregulation of such non-coding transcribes might also affect tumor phenotypes. Indeed, to date, lncRNAs have been reported to affect diverse biological processes through the regulation of mRNA stability, RNA splicing, chromatin structure, and miRNA-mediated gene regulation by acting as miRNA sponges...
August 4, 2017: Cancer Science
https://www.readbyqxmd.com/read/28772289/association-of-mismatch-repair-mutation-with-age-at-cancer-onset-in-lynch-syndrome-implications-for-stratified-surveillance-strategies
#17
Neil A J Ryan, Julie Morris, Kate Green, Fiona Lalloo, Emma R Woodward, James Hill, Emma J Crosbie, D Gareth Evans
Importance: Lynch syndrome is caused by dominantly inherited germline mutations that predispose individuals to colorectal, endometrial, ovarian, and other cancers through inactivation of the cellular mismatch repair system. Lynch syndrome-associated cancers are amenable to surveillance strategies that may improve survival. The age at which surveillance should start is disputed. Objective: To determine whether mutated gene and type of mutation influence age at onset of Lynch syndrome-associated cancers...
August 3, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28768194/a-conserved-splicing-silencer-dynamically-regulates-o-glcnac-transferase-intron-retention-and-o-glcnac-homeostasis
#18
Sung-Kyun Park, Xiaorong Zhou, Kathryn E Pendleton, Olga V Hunter, Jennifer J Kohler, Kathryn A O'Donnell, Nicholas K Conrad
Modification of nucleocytoplasmic proteins with O-GlcNAc regulates a wide variety of cellular processes and has been linked to human diseases. The enzymes O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) add and remove O-GlcNAc, but the mechanisms regulating their expression remain unclear. Here, we demonstrate that retention of the fourth intron of OGT is regulated in response to O-GlcNAc levels. We further define a conserved intronic splicing silencer (ISS) that is necessary for OGT intron retention. Deletion of the ISS in colon cancer cells leads to increases in OGT, but O-GlcNAc homeostasis is maintained by concomitant increases in OGA protein...
August 1, 2017: Cell Reports
https://www.readbyqxmd.com/read/28765883/-corrigendum-transcriptome-sequencing-of-human-breast-cancer-reveals-aberrant-intronic-transcription-in-amplicons-and-dysregulation-of-alternative-splicing-with-major-therapeutic-implications
#19
(no author information available yet)
After the publication of the article, the authors retrospectively noted that the name of Dr Dawn Jones, a postdoctoral researcher in the laboratory of Professor Christine Gosden, should have been added to the authors' list, whose contribution to the study greatly augmented the exploration of all the RNA products via adoption of the RNASeq (Illumina) methodology. All the existing authors agree to the inclusion of Dr Jones as a co‑author, with the exception of Derek Gardener, who has retired from the Institute and is no longer contactable by e-mail (although we are confident that he would not raise any objection)...
September 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28765161/the-interplay-between-epigenetic-changes-and-the-p53-protein-in-stem-cells
#20
REVIEW
Arnold J Levine, Shelley L Berger
Epigenetic programs regulate the development and maintenance of organisms over a lifetime. These programs are carried out through chemical modifications of DNA and proteins such as histones and transcription factors. These epigenetic modifications are less stable than genetic alterations and even reversible under a variety of circumstances, such as developmental changes, regeneration of tissues, cell divisions, aging, and pathological conditions observed in many cancers. The p53 protein not only enforces the stability of the genome by the prevention of genetic alterations in cells but also plays a role in regulating the epigenetic changes that can occur in cells...
June 15, 2017: Genes & Development
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