Long non-coding RNA NEAT1 targeting impairs the DNA repair machinery and triggers anti-tumor activity in multiple myeloma

Leukemia, Published online: 19 August 2019; doi:10.1038/s41375-019-0542-5Long non-coding RNA NEAT1 targeting impairs the DNA repair machinery and triggers anti-tumor activity in multiple myeloma
Source: Leukemia - Category: Hematology Authors: Source Type: research

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In this study, we utilized proximity-based labeling (BioID) combined with label-free quantitative MS to identify high confidence NSD2 interacting partners in MM cells. The top 24 proteins identified were involved in maintaining chromatin structure, transcriptional regulation, RNA pre-spliceosome assembly, and DNA damage. Among these, an important DNA damage regulator, poly(ADP-ribose) polymerase 1 (PARP1), was discovered. PARP1 and NSD2 have been found to be recruited to DNA double strand breaks upon damage and H3K36me2 marks are enriched at damage sites. We demonstrate that PARP1 regulates NSD2 via PARylation upon oxidati...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Genomics and Proteomics Source Type: research
In this study, we reviewed major human studies on the health risks of radiation exposure and showed that sex-related factors may potentially influence the long-term response to radiation exposure. Available data suggest that long-term radiosensitivity in women is higher than that in men who receive a comparable dose of radiation. The report on the biological effects of ionizing radiation (BEIR VII) published in 2006 by the National Academy of Sciences, United States emphasized that women may be at significantly greater risk of suffering and dying from radiation-induced cancer than men exposed to the same dose of radiation....
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Antonio Lucena-Cacace1, Masayuki Umeda1, Lola E. Navas2,3 and Amancio Carnero2,3* 1Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan 2CIBERONC, ISCIII, Madrid, Spain 3Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío (HUVR), CSIC, Universidad de Sevilla, Sevilla, Spain Glioma Cancer Stem-Like Cells (GSCs) are a small subset of CD133+ cells with self-renewal properties and capable of initiating new tumors contributing to Glioma progression, maintenance, hierarchy, and complexity. GSCs are highly res...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusion and Future Perspectives This review illustrates our current knowledge of USP7, including its source and characterization, structure, binding partners and substrates in various biological processes. Besides, how USP7 regulates various aspects of a cell under both normal and pathological states are elaborated in detail. As the processes of ubiquitination and deubiquitination are extremely dynamic and context-specific, a series of studies have linked USP7 to different cancers. The biology, particularly the immune oncology mechanisms, reveal that USP7 inhibitors would be useful drugs, thus it is vital to develop hi...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusions The concept of osteoimmunology is aging well, almost 20 years since the term was coined. This way of interpreting bone and the immune system has been steadily providing new insights about how the two of them operate and cooperate. As an example, the role of pro-inflammatory cytokines in promoting osteoclastogenesis, and the many parallelisms between immune cells and osteoclasts have proved crucial to understand the biology of these giant bone-eating cells. Intriguingly, the control mechanisms between bone and the immune system are complex, tightly interconnected, and involve many players. The underlying comple...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
Discussion In this section, we discuss the mechanisms responsible for lymphomagenesis in the various inborn errors of immunity and provide an overview of the treatment. Defects in Immune Responses That Predispose to Lymphomagenesis in PIDDs The complex immune mechanisms and their interplay that predisposes to neoplastic transformation of B or T cells and development of lymphomas in PIDD patients has not been fully elucidated. However, it is expected that the etiology in most cases is multifactorial and related to a dynamic regulation of immune response and environmental triggers (Figure 3). An underlying intrinsic susce...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
This study was supported by the Shanghai Sailing Program [grant number 17YF1425200, 2017]; Chinese National Natural Science Funding [grant number 81702249, 2017]; Science and Technology Commission of Shanghai Municipality [grant number 17511103403, 2017]; The funder has no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Acknowledgments We acknowledge the ex...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Yi He†, Wenyong Long† and Qing Liu* Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China Super-enhancers (SEs) refer to large clusters of enhancers that drive gene expressions. Recent data has provided novel insights in elucidating the roles of SEs in many diseases, including cancer. Many mechanisms involved in tumorigenesis and progression, ranging from internal gene mutation and rearrangement to external damage and inducement, have been demonstrated to be highly associated with SEs. Moreover, translocation, formation, deletion, or duplication of SEs themselves co...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Introduction We identified an integral role of bone marrow (BM) plasmacytoid dendritic cells (pDCs) in multiple myeloma (MM) pathogenesis. Specifically, we found increased numbers pDCs in MM BM vs normal BM. pDCs protect tumor cells from therapy-induced cytotoxicity; promote tumor growth and survival, as well as suppress immune responses (Chauhan et al, Cancer Cell 2009, 16:309-323). Aberrant pDC function is evidenced in their interactions not only with MM cells, but also with immune effector T cells and NK cells in the MM BM milieu (Ray et al, Leukemia 2015, 29:1441-1444). Directly targeting pDC interactions with MM and i...
Source: Blood - Category: Hematology Authors: Tags: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Immunological Aspects and the Microenvironment in Myeloma Pathogenesis Source Type: research
Genetic alterations of epigenetic regulators that alter the repressive trimethylation of lysine 27 on histone H3 (H3K27me3) are a recurrent feature in cancer. The histone demethylase UTX/KDM6A Is mutated in ~5% of multiple myeloma (MM) at diagnosis and is commonly absent in MM cell lines, derived from patients with advanced disease. KDM6A forms a complex containing H3K4 specific methyltransferases KMT2D and KMT2C, the histone acetyltransferase CBP/p300 and SWI/SNF chromatin-remodelers. Collectively the complex adds activation marks on histones and removes the gene repression associated H3K37me mark at enhancers. Removal of...
Source: Blood - Category: Hematology Authors: Tags: Targeting Epigenetic Regulation in Myeloma Source Type: research
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