Download or read book Elucidating Mechanisms of Alternative Splicing in Cancer and Cellular Stress written by Matias Ignacio Montes Serey and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alternative splicing of the pre-mRNA is an essential post-transcriptional process in eukaryotes that generates multiple protein isoforms from a single gene. However, this process can be disrupted by mutations leading to several diseases including cancer. One such example is the oncogene and negative regulator of p53 Mouse Double Minute 2 homolog (MDM2), which undergoes alternative splicing to produce a splice isoform that has novel implications in cancer development. MDM2-Alt1 comprised of coding exons 3 and 12, is highly expressed in several cancers including those of the breast, liposarcomas, high-grade gliomas and rhabdomyosarcomas (RMS), and can be induced by genotoxic stress. Another good example of cancer-related aberrant alternative splicing, is the insulin receptor gene (INSR), comprised of 22 exons, and that skipping of the exon 11 allows the production of the IR-A splice isoform. Overexpression of the IR-A isoform compared to the full-length IR-B isoform, has been reported in several cancers including RMS, osteosarcoma, breast cancer, prostate cancer and hepatocellular carcinoma. Understanding of the splicing mechanisms of these two genes is crucial to improve current cancer therapies. In this work we report that SRSF2 positively regulates the alternative splicing of MDM2 and that its binding to the exon 11 can be modulated to generate novel mouse model for cancer studies. Furthermore, we show a novel and unique regulatory mechanism of splicing wherein a nuclear microRNA, miR-29b, influences the alternative splicing of MDM2 by directly binding to the MDM2 pre-mRNA. We show that miR-29b is downregulated by genotoxic stress, a similar characteristic of cancer cells. Finally, we study the usage of antisense oligonucleotides (ASOs) as cancer therapies, by blocking the binding of the CUG-BP1 (CUG Binding Protein 1) splicing factor with an ASO, we promote the alternative splicing of the IR-B isoform which decreases cell proliferation and angiogenesis. Moreover, modulation of the MBNL1 (Muscleblind Like 1) intronic splicing enhancer in the intron 11 of the INSR, set the foundation for a novel mouse model to study this aberrant alternative splicing. Overall, our study underscores the importance of understanding alternative splicing in cancer research, moreover, it expands the knowledge regarding the complex splicing mechanisms involved in disease and finally set the foundations for the design of novel and effective splice-switching cancer therapies.
Download or read book Regulation of Alternative Splicing written by Philippe Jeanteur and published by Springer Science & Business Media. This book was released on 2002-10-21 with total page 272 pages. Available in PDF, EPUB and Kindle. Book excerpt: The discovery in 1977 that genes are split into exons and introns has done away with the one gene - one protein dogma. Indeed, the removal of introns from the primary RNA transcript is not necessarily straightforward since there may be optional pathways leading to different messenger RNAs and consequently to different proteins. Examples of such an alternative splicing mechanism cover all fields of biology. Moreover, there are plenty of occurrences where deviant splicing can have pathological effects. Despite the high number of specific cases of alternative splicing, it was not until recently that the generality and extent of this phenomenon was fully appreciated. A superficial reading of the preliminary sequence of the human genome published in 2001 led to the surprising, and even deceiving to many scientists, low number of genes (around 32,000) which contrasted with the much higher figure around 150,000 which was previously envisioned. Attempts to make a global assessment of the use of alternative splicing are recent and rely essentially on the comparison of genomic mRNA and EST sequences as reviewed by Thanaraj and Stamm in the first chapter of this volume. Most recent estimates suggest that 40-60% of human genes might be alternatively spliced, as opposed to about 22% for C. elegans.
Download or read book Mechanisms of Carcinogenesis written by Elizabeth K. Weisburger and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 210 pages. Available in PDF, EPUB and Kindle. Book excerpt: but also the possibility of intervention in specific stages. In Human behavior, including stress and other factors, plays an important role in neoplasia, although too little is known addition, variables which affect cancer development as well on the reasons for such development. Carcinogens, which as some endogenous factors can be better delineated help initiate the neoplastic process, may be either synthetic through such investigations. The topics of this volume encompass premalignant non or naturally-occurring. Cancer causation may be ascribed to invasive lesions, species-specific aspects of carcinogenicity, certain chemicals, physical agents, radioactive materials, viruses, parasites, the genetic make-up of the organism, and radiation, viruses, a quantum theory of carinogenesis, onco bacteria. Humans, eumetazoan animals and vascular plants genes, and selected environmental carcinogens. are susceptible to the first six groups of cancer causes, whe reas the last group, bacteria, seems to affect only vascular plants. Neoplastic development may begin with impairment ofJmdy defenses by a toxic material (carcinogen) which acts as an initiator, followed by promotion and progression to an overt neoplastic state. Investigation of these processes Series Editor Volume Editor allows not only a better insight into the mechanism of action Hans E. Kaiser Elizabeth K. Weisburger vii ACKNOWLEDGEMENT Inspiration and encouragement for this wide ranging project on cancer distribution and dissemination from a comparative biological and clinical point of view, was given by my late friend E. H. Krokowski.
Download or read book The Unfolded Protein Response in Cancer written by Robert Clarke and published by Springer. This book was released on 2019-03-01 with total page 220 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume presents state-of-the-art information on each of the arms of the unfolded protein response (UPR), how their activation/repression are regulated, integrated, and coordinated, how UPR components affect cancer cell biology and responsiveness to therapeutic interventions, and how UPR components/activities offer potentially novel targets for drug discovery, repurposing, and development. The volume will provide the most recent information on the signaling and regulation of the UPR, explore examples of how the UPR and/or specific components contribute to cancer biology, and identify and explore specific examples of potently new actionable targets for drug discovery and development from within the UPR and its regulation. Unique to the volume will be a specific focus on the UPR and its role in cancer biology, as well as a discussion of the role of the UPR in drug responses and resistance in cancer.
Download or read book How Tobacco Smoke Causes Disease written by United States. Public Health Service. Office of the Surgeon General and published by . This book was released on 2010 with total page 728 pages. Available in PDF, EPUB and Kindle. Book excerpt: This report considers the biological and behavioral mechanisms that may underlie the pathogenicity of tobacco smoke. Many Surgeon General's reports have considered research findings on mechanisms in assessing the biological plausibility of associations observed in epidemiologic studies. Mechanisms of disease are important because they may provide plausibility, which is one of the guideline criteria for assessing evidence on causation. This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke. This evidence is relevant to understanding how smoking causes disease, to identifying those who may be particularly susceptible, and to assessing the potential risks of tobacco products.
Download or read book Metallo Drugs Development and Action of Anticancer Agents written by Astrid Sigel and published by Walter de Gruyter GmbH & Co KG. This book was released on 2018-02-05 with total page 588 pages. Available in PDF, EPUB and Kindle. Book excerpt: Volume 18, entitled Metallo-Drugs: Development and Action of Anticancer Agents of the series Metal Ions in Life Sciences centers on biological, medicinal inorganic chemistry. The serendipitous discovery of the antitumor activity of cis-diamminodichloroplatinum(II) (cisplatin) by Barnett Rosenberg in the 1960s is a landmark in metallodrug-based chemotherapy. The success of cisplatin in the clinic, followed by oxaliplatin and carboplatin, along with their drawbacks relating mainly to resistance development and severe toxicity, initiated research on polynuclear platinum complexes and on Pt(IV) complexes as prodrugs. Furthermore, the indicated shortcomings led to the exploration of other transition and main group metal ions, among them Ru(II/III), Au(I/III), Ti(IV), V(IV/V), and Ga(III) including also the essential metal ions Fe(II/III), Cu(I/II), and Zn(II). Ionic as well as covalent and non-covalent interactions between structurally very different complexes and biomolecules like nucleic acids, proteins, and carbohydrates are studied and discussed with regard to their possible anticancer actions. Hence, MILS-18 summarizes the research at the forefront of medicinal inorganic chemistry, including studies on the next-generation, tailor-made anticancer drugs. All this and more is treated in an authoritative and timely manner in the 17 stimulating chapters of this book, written by 39 internationally recognized experts from 10 nations (from the US via Europe to China and Australia). The impact of this vibrant research area is manifested by more than 2700 references, nearly 150 illustrations (more than half in color) and several comprehensive tables. Metallo-Drugs: Development and Action of Anticancer Agents is an essential resource for scientists working in the wide range from enzymology, material sciences, analytical, organic, and inorganic biochemistry all the way through to medicine including the clinic ... not forgetting that it also provides excellent information for teaching.
Download or read book Epigenetic Mechanisms of Gene Regulation written by Vincenzo E. A. Russo and published by . This book was released on 1996 with total page 716 pages. Available in PDF, EPUB and Kindle. Book excerpt: Many inheritable changes in gene function are not explained by changes in the DNA sequence. Such epigenetic mechanisms are known to influence gene function in most complex organisms and include effects such as transposon function, chromosome imprinting, yeast mating type switching and telomeric silencing. In recent years, epigenetic effects have become a major focus of research activity. This monograph, edited by three well-known biologists from different specialties, is the first to review and synthesize what is known about these effects across all species, particularly from a molecular perspective, and will be of interest to everyone in the fields of molecular biology and genetics.
Download or read book Scientific Frontiers in Developmental Toxicology and Risk Assessment written by National Research Council and published by National Academies Press. This book was released on 2000-12-21 with total page 348 pages. Available in PDF, EPUB and Kindle. Book excerpt: Scientific Frontiers in Developmental Toxicology and Risk Assessment reviews advances made during the last 10-15 years in fields such as developmental biology, molecular biology, and genetics. It describes a novel approach for how these advances might be used in combination with existing methodologies to further the understanding of mechanisms of developmental toxicity, to improve the assessment of chemicals for their ability to cause developmental toxicity, and to improve risk assessment for developmental defects. For example, based on the recent advances, even the smallest, simplest laboratory animals such as the fruit fly, roundworm, and zebrafish might be able to serve as developmental toxicological models for human biological systems. Use of such organisms might allow for rapid and inexpensive testing of large numbers of chemicals for their potential to cause developmental toxicity; presently, there are little or no developmental toxicity data available for the majority of natural and manufactured chemicals in use. This new approach to developmental toxicology and risk assessment will require simultaneous research on several fronts by experts from multiple scientific disciplines, including developmental toxicologists, developmental biologists, geneticists, epidemiologists, and biostatisticians.
Download or read book Alternative Splicing and Disease written by Philippe Jeanteur and published by Springer Science & Business Media. This book was released on 2006-10-04 with total page 265 pages. Available in PDF, EPUB and Kindle. Book excerpt: Splicing of primary RNA transcript is a quasi-systematic step of gene expression in higher organisms. This is the first book to highlight the medical implications, i.e. diseases, caused by alternative splicing. Alternative splicing not only vastly increases protein diversity but also offers numerous opportunities for aberrant splicing events with pathological consequences. The book also outlines possible targets for therapy.
Download or read book Molecular mechanisms of cellular stress responses in cancer and their therapeutic implications written by Megan Chircop and published by Frontiers Media SA. This book was released on 2015-03-06 with total page 160 pages. Available in PDF, EPUB and Kindle. Book excerpt: In response to stress, cells can activate a myriad of signalling pathways to bring about a specific cellular outcome, including cell cycle arrest, DNA repair, senescence and apoptosis. This response is pivotal for tumour suppression as all of these outcomes result in restriction of the growth and/or elimination of damaged and pre-malignant cells. Thus, a large number of anti-cancer agents target specific components of stress response signalling pathways with the aim of causing tumour regression by stimulating cell death. However, the efficacy of these agents is often impaired due to mutations in genes that are involved in these stress-responsive signalling pathways and instead the oncogenic potential of a cell is increased leading to the initiation and/or progression of tumourigenesis. Moreover, these genetic defects can increase or contribute to resistance to chemotherapeutic agents and/or radiotherapy. Modulating the outcome of cellular stress responses towards cell death in tumour cells without affecting surrounding normal cells is thus one of the ultimate aims in the development of new cancer therapeutics. To achieve this aim, a detailed understanding of cellular stress response pathways and their aberrations in cancer is required. This Research topic aims to reflect the broadness and complexity of this important area of cancer research.
Download or read book RNA Splicing and Backsplicing Disease and Therapy written by Rosanna Asselta and published by Frontiers Media SA. This book was released on 2020-12-24 with total page 197 pages. Available in PDF, EPUB and Kindle. Book excerpt: This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.
Download or read book Innovative Medicine written by Kazuwa Nakao and published by Springer. This book was released on 2015-10-13 with total page 330 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is devoted to innovative medicine, comprising the proceedings of the Uehara Memorial Foundation Symposium 2014. It remains extremely rare for the findings of basic research to be developed into clinical applications, and it takes a long time for the process to be achieved. The task of advancing the development of basic research into clinical reality lies with translational science, yet the field seems to struggle to find a way to move forward. To create innovative medical technology, many steps need to be taken: development and analysis of optimal animal models of human diseases, elucidation of genomic and epidemiological data, and establishment of “proof of concept”. There is also considerable demand for progress in drug research, new surgical procedures, and new clinical devices and equipment. While the original research target may be rare diseases, it is also important to apply those findings more broadly to common diseases. The book covers a wide range of topics and is organized into three complementary parts. The first part is basic research for innovative medicine, the second is translational research for innovative medicine, and the third is new technology for innovative medicine. This book helps to understand innovative medicine and to make progress in its realization.
Download or read book Transcription and Splicing written by B. D. Hames and published by Oxford University Press, USA. This book was released on 1988 with total page 238 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book gives a co-ordinated review of our present knowledge of eukaryotic RNA synthesis.
Download or read book Stress Activated Protein Kinases written by Francesc Posas and published by Springer Science & Business Media. This book was released on 2008-01-24 with total page 322 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this book leading researchers in the field discuss the state-of-the-art of many aspects of SAPK signaling in various systems from yeast to mammals. These include various chapters on regulatory mechanisms as well as the contribution of the SAPK signaling pathways to processes such as gene expression, metabolism, cell cycle regulation, immune responses and tumorigenesis. Written by international experts, the book will appeal to cell biologists and biochemists.
Download or read book Colloquium on Molecular Kinesis in Cellular Function and Plasticity written by Henri Tiedge and published by National Academies Press. This book was released on 2002 with total page 120 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book The Role of Sphingolipids in Cancer Development and Therapy written by and published by Academic Press. This book was released on 2012-12-31 with total page 313 pages. Available in PDF, EPUB and Kindle. Book excerpt: Advances in Cancer Research provides invaluable information on the exciting and fast-moving field of cancer research. This thematic volume looks at "The Role of Sphingolipids in Cancer Development and Therapy" Provides invaluable information on the exciting and fast-moving field of cancer research This thematic volume looks at "The Role of Sphingolipids in Cancer Development and Therapy" Outstanding and original reviews
Download or read book The Transformed Phenotype written by Arnold Jay Levine and published by Cold Spring Harbor Laboratory Press. This book was released on 1984 with total page 302 pages. Available in PDF, EPUB and Kindle. Book excerpt:
