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Epigenetics in endometrial carcinogenesis - part 2: histone modifications, chromatin remodeling and noncoding rnas

EPIGENOMICS 2017年第6期9卷 873-892页

作者： Bartosch, Carla Lopes, Jose Manuel Jeronimo, Carmen Portuguese Oncol Inst Porto IPO Porto Dept Pathol Oporto Portugal Portuguese Oncol Inst Porto Canc Biol & Epigenet Grp Res Ctr CI IPOP Oporto Portugal Univ Porto Med Fac Dept Pathol & Oncol Oporto Portugal Porto Comprehens Canc Ctr Oporto Portugal Ctr Hosp Sao Joao Dept Pathol Oporto Portugal Univ Porto IPATIMUP Inst Mol Pathol & Immunol Oporto Portugal Univ Porto Inst Invest & Inovacao Saude I3S Oporto Portugal Univ Porto Inst Biomed Sci Abel Salazar ICBAS Dept Pathol & Mol Immunol Oporto Portugal

Carcinogenesis is a multistep multifactorial process that involves the accumulation of genetic and epigenetic alterations. In the past two decades, there has been an exponential growth of knowledge establishing the importance of epigenetic changes in cancer. Our work focused on reviewing the main role of epigenetics in the pathogenesis of endometrial carcinoma, highlighting the reported results concerning each epigenetic mechanistic layer. In a previous review, we assessed DNA methylation alterations. The present review examines the contribution of histone modifications, chromatin remodeling and noncoding rna alterations for endometrial carcinogenesis.

关键词： chromatin remodeling endometrial carcinoma epigenetics histone noncoding rna

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Recent trends on the role of epigenomics, metabolomics and noncoding rnas in rationalizing mood stabilizing treatment

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PHARMACOGENOMICS 2018年第2期19卷 129-143页

作者： Pisanu, Claudia Katsila, Theodora Patrinos, George P. Squassina, Alessio Univ Cagliari Sect Neurosci & Clin Pharmacol Dept Biomed Sci Cagliari Italy Uppsala Univ Unit Funct Pharmacol Dept Neurosci Uppsala Sweden Univ Patras Sch Hlth Sci Dept Pharm Patras Greece United Arab Emirates Univ Coll Med & Hlth Sci Dept Pathol Al Ain U Arab Emirates Dalhousie Univ Dept Psychiat Halifax NS Canada

y Mood stabilizers are the cornerstone in treatment of mood disorders, but their use is characterized by high interindividual variability. This feature has stimulated intensive research to identify predictive biomarkers of response and disentangle the molecular bases of their clinical efficacy. Nevertheless, findings from studies conducted so far have only explained a small proportion of the observed variability, suggesting that factors other than DNA variants could be involved. A growing body of research has been focusing on the role of epigenetics and metabolomics in response to mood stabilizers, especially lithium salts. Studies from these approaches have provided new insights into the molecular networks and processes involved in the mechanism of action of mood stabilizers, promoting a systems-level multiomics synergy. In this article, we reviewed the literature investigating the involvement of epigenetic mechanisms, noncoding rnas and metabolomic modifications in bipolar disorder and the mechanism of action and clinical efficacy of mood stabilizers.

关键词： carbamazepine epigenetics lithium metabolomics mood stabilizers noncoding rna valproate

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The role and mechanism of noncoding rnas in regulation of metabolic reprogramming in hepatocellular carcinoma

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INTErnaTIONAL JOUrnaL OF CANCER 2022年第3期151卷 337-347页

作者： Liao, Wenwei Du, Jinpeng Wang, Zhen Feng, Qingbo Liao, Mingheng Liu, Huixian Yuan, Kefei Zeng, Yong Sichuan Univ West China Hosp State Key Lab Biotherapy Dept Liver Surg & Liver Transplantat Chengdu Peoples R China Sichuan Univ West China Hosp Ctr Canc Chengdu Peoples R China Collaborat Innovat Ctr Biotherapy Chengdu Peoples R China Sun Yat Sen Univ Affiliated Hosp 1 Dept Postanesthesia Care Unit Guangzhou Peoples R China Sun Yat Sen Univ Affiliated Hosp 1 Surg Anesthesia Ctr Guangzhou Peoples R China

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Metabolic reprogramming is considered to be an important hallmark of cancer. Emerging studies have demonstrated that noncoding rnas (ncrnas) are closely associated with metabolic reprogramming of HCC. Ncrnas can directly regulate the expressions or functions of metabolic enzymes or indirectly regulate the metabolism of HCC cells through some vital signaling pathways. Until now, the mechanisms of HCC development and progression remain largely unclear, and understanding the regulatory mechanism of ncrnas on metabolic reprogramming of HCC may provide an important basis for breakthrough progress in the treatment of HCC. In this review, we summarize the ncrnas involved in regulating metabolic reprogramming of HCC. Specifically, the regulatory roles of ncrnas in glucose, lipid and amino acid metabolism are elaborated. In addition, we discuss the molecular mechanism of ncrnas in regulation of metabolic reprogramming and possible therapeutic strategies that target the metabolism of cancer cells by modulating the expressions of specific ncrnas.

关键词： circrna hepatocellular carcinoma lncrna metabolic reprogramming noncoding rna

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Long noncoding rnas MEG3, TUG1, and hsa-miR-21-3p Are Potential Diagnostic Biomarkers for Coronary Artery Disease

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MOLECULAR BIOLOGY 2023年第6期57卷 1186-1198页

作者： Abdelgawad, M. Abdallah, H. Y. Fareed, A. Ahmed, A. E. Beni Suef Univ Fac Postgrad studies Adv Sci Biotechnol & Life Sci Dept Bani Suwayf 62511 Egypt Suez Canal Univ Fac Med Dept Histol & Cell Biol Genet Unit Ismailia 41522 Egypt Suez Canal Univ Fac Med Ctr Excellence Mol & Cellular Med Ismailia 41522 Egypt Suez Canal Univ Fac Med Dept Cardiol Ismailia 41522 Egypt

Peripheral blood biomarkers are of particular importance to diagnose certain diseases including coronary artery disease (CAD) due to their non-invasiveness. Investigating the expression of noncoding rnas (ncrnas) paves the way to early disease diagnosis, prognosis, and treatment. Consequently, in this research, we aimed to investigate a panel of ncrnas as potential biomarkers in patients with coronary artery disease. Two different groups have been designed (control and CAD). All participants were subjected to interviews and clinical examinations. Peripheral blood samples were collected, and plasma was extracted. At the same time, target ncrnas have been selected based on literature review and bioinformatic analysis, and later they underwent investigation using quantitative real-time PCR. The selected panel encompassed the long non-coding rnas (lncrnas) MEG3, TUG1, and SRA1, and one related microrna (mirna): hsa-miR-21-3p. We observed statistically significant upregulation in MEG3, TUG1, and hsa-miR21-3p in CAD patients compared to control participants (p-value < 0.01). Nevertheless, SRA1 exhibited downregulation with no statistical significance (p-value > 0.05). All ncrnas under study displayed a significantly strong correlation with disease incidence, age, and smoking. Network construction revealed a strong relationship between MEG3 and TUG1. ROC analysis indicated high potentiality for hsa-miR-21-3p to be a promising biomarker for CAD. Moreover, MEG3 and TUG1 displayed distinguished diagnostic discrimination but less than hsa-miR-21-3p, all of them exhibited strong statistical significance differences between CAD and control groups. Conclusively, this research pinpointed that MEG3, TUG1, and hsa-miR-21-3p are potential biomarkers of CAD incidence and diagnosis.

关键词： coronary artery disease MEG3 TUG1 noncoding rna lncrna biomarker

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Long noncoding rnas: Lessons from genomic imprinting

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BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS 2016年第1期1859卷 102-111页

作者： Kanduri, Chandrasekhar Univ Gothenburg Sahlgrenska Acad Inst Biomed Dept Med Genet S-40530 Gothenburg Sweden

Genomic imprinting has been a great resource for studying transcriptional and post-transcriptional-based gene regulation by long noncoding rnas (lncrnas). In this article, I overview the functional role of intergenic lncrnas (H19, IPW, and MEG3), antisense lncrnas (Kcnq1ot1, Airn, Nespas, Ube3a-ATS), and enhancer lncrnas (IG-DMR ernas) to understand the diverse mechanisms being employed by them in cis and/or trans to regulate the parent-of-origin specific expression of target genes. Recent evidence suggests that some of the Incrnas regulate imprinting by promoting intra-chromosomal higher-order chromatin compartmentalization, affecting replication timing and subnuclear positioning. Whereas others act via transcriptional occlusion or transcriptional collision-based mechanisms. By establishing genomic imprinting of target genes, the lncrnas play a critical role in important biological functions, such as placental and embryonic growth, pluripotency maintenance, cell differentiation, and neural-related functions such as synaptic development and plasticity. An emerging consensus from the recent evidence is that the imprinted lncrnas fine-tune gene expression of the protein-coding genes to maintain their dosage in cell. Hence, lncrnas from imprinted clusters offer insights into their mode of action, and these mechanisms have been the basis for uncovering the mode of action of lncrnas in several other biological contexts. This article is part of a Special Issue entitled: Clues to long noncoding rna taxonomy, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa. (C) 2015 Elsevier B.V. All rights reserved.

关键词： Long noncoding rna Genomic imprinting Chromatin Epigenetics noncoding rna lncrna

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Identification of protein-coding and intronic noncoding rnas down-regulated in clear cell renal carcinoma

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MOLECULAR CARCINOGENESIS 2008年第10期47卷 757-767页

作者： Brito, Glauber Costa Fachel, Angela A. Vettore, Andre Luiz Vignal, Giselle M. Gimba, Etel R. P. Campos, Franz S. Barcinski, Marcello A. Verjovski-Almeida, Sergio Reis, Eduardo M. Univ Sao Paulo Inst Quim Dept Bioquim BR-05508 Sao Paulo Brazil Univ Fed Sao Paulo Sao Paulo Brazil Hosp Canc Inst Nacl Canc MS Rio De Janeiro Brazil

The clear cell subtype of renal cell carcinoma (RCC) is the most lethal and prevalent cancer of the urinary system. To investigate the molecular changes associated with malignant transformation in clear cell RCC, the gene expression profiles of matched samples of tumor and adjacent non-neoplastic tissue were obtained from six patients. A custom-built cDNA microarray platform was used, comprising 2292 probes that map to exons of genes and 822 probes for noncoding rnas mapping to intronic regions. Intronic transcription was detected in all normal and neoplastic renal tissues. A subset of 55 transcripts was significantly down-regulated in clear cell RCC relative to the matched nontumor tissue as determined by a combination of two statistical tests and leave-one-out patient cross-validation. Among the down-regulated transcripts, 49 mapped to untranslated or coding exons and 6 were intronic relative to known exons of protein-coding genes. Lower levels of expression of SIN3B, TRIP3, SYNJ2BP and NDE1 (P<0.02), and of intronic transcripts derived from SND1 and ACTN4 loci (P<0.05), were confirmed in clear cell RCC by Real-time RT-PCR. A subset of 25 transcripts was deregulated in additional six nonclear cell RCC samples, pointing to common transcriptional alterations in RCC irrespective of the histological subtype or differentiation state of the tumor. Our results indicate a novel set of tumor suppressor gene candidates, including noncoding intronic rnas, which may play a significant role in malignant transformations of normal renal cells. (C) 2008 Wiley-Liss, Inc.

关键词： clear cell renal cell carcinoma noncoding rna intronic transcription cDNA microarray tumor suppressor

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Epigenetics of imprinted long noncoding rnas

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EPIGENETICS 2009年第5期4卷 277-286页

作者： Mohammad, Faizaan Mondal, Tanmoy Kanduri, Chandrasekhar Uppsala Univ Dept Genet & Pathol Rudbeck Lab Uppsala Sweden

It is becoming increasingly evident that noncoding rna (ncrna) constitutes an important component of chromatin and that ncrna has a critical role in organizing the chromatin architecture and epigenetic memory by acting as an interface with the chromatin modifying machinery. Xist is the only rna that has been shown to regulate gene expression by modulating chromatin structure using a multilayered silencing pathway. Recent emerging evidence indicates that long ncrnas such as Kcnq1ot1 and Air which map to the Kcnq1 and Igf2r imprinted gene clusters, respectively, mediate the transcriptional silencing of multiple genes by interacting with chromatin and recruiting the chromatin modifying machinery. Though there are some parallels in the mechanistic actions of Kcnq1ot1 and Air, they seem to differ greatly in the way they achieve the silencing of overlapping and nonoverlapping genes. By reviewing the latest available evidence, we propose that Kcnq1ot1 rna itself seems to play a critical role in the bidirectional silencing of genes in the Kcnq1 domain, thus resembling the Xist rna;whereas in the case of Air, the act of transcription plays a critical role in the silencing of the overlapping gene, whilst Air rna itself mediates the silencing of nonoverlapping genes in a fashion similar to Kcnq1ot1 and Xist rnas.

关键词： noncoding rna epigenetics chromatin genomic imprinting X-chromosome inactivation Kcnq1ot1 air xist

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Distinguishing the immunostimulatory properties of noncoding rnas expressed in cancer cells

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2015年第49期112卷 15154-15159页

作者： Tanne, Antoine Muniz, Luciana R. Puzio-Kuter, Anna Leonova, Katerina I. Gudkov, Andrei V. Ting, David T. Monasson, Remi Cocco, Simona Levine, Arnold J. Bhardwaj, Nina Greenbaum, Benjamin D. Icahn Sch Med Mt Sinai Tisch Canc Inst Dept Med Hematol & Med Oncol New York NY 10029 USA Rutgers Canc Inst New Jersey New Brunswick NJ 08903 USA Roswell Pk Canc Inst Buffalo NY 14263 USA Massachusetts Gen Hosp Charlestown MA 02129 USA CNRS Lab Phys Theor F-75005 Paris France Ecole Normale Super F-75005 Paris France CNRS Lab Phys Stat F-75005 Paris France Princeton Univ Sch Nat Sci Simons Ctr Syst Biol Inst Adv Study Princeton NJ 08540 USA Icahn Sch Med Mt Sinai Dept Pathol New York NY 10029 USA

Recent studies have demonstrated abundant transcription of a set of noncoding rnas (ncrnas) preferentially within tumors as opposed to normal tissue. Using an approach from statistical physics, we quantify global transcriptome-wide motif use for the first time, to our knowledge, in human and murine ncrnas, determining that most have motif use consistent with the coding genome. However, an outlier subset of tumor-associated ncrnas, typically of recent evolutionary origin, has motif use that is often indicative of pathogen-associated rna. For instance, we show that the tumor-associated human repeat human satellite repeat II (HSATII) is enriched in motifs containing CpG dinucleotides in AU-rich contexts that most of the human genome and human adapted viruses have evolved to avoid. We demonstrate that a key subset of these ncrnas functions as immunostimulatory "self-agonists" and directly activates cells of the mononuclear phagocytic system to produce proinflammatory cytokines. These ncrnas arise from endogenous repetitive elements that are normally silenced, yet are often very highly expressed in cancers. We propose that the innate response in tumors may partially originate from direct interaction of immunogenic ncrnas expressed in cancer cells with innate pattern recognition receptors, and thereby assign a previously unidentified danger-associated function to a set of dark matter repetitive elements. These findings potentially reconcile several observations concerning the role of ncrna expression in cancers and their relationship to the tumor microenvironment.

关键词： noncoding rna genome evolution cancer immunology

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Emerging Role of Micrornas and Long noncoding rnas in Respiratory Disease

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CHEST 2014年第1期146卷 193-204页

作者： Booton, Richard Lindsay, Mark A. Univ Manchester Inst Inflammat & Repair Manchester Lancs England Univ S Manchester Hosp Manchester Acad Hlth Sci Ctr Manchester M20 8LR Lancs England Univ S Manchester Hosp North West Lung Ctr Manchester M20 8LR Lancs England Univ Bath Dept Pharm & Pharmacol Bath BA2 7AY Avon England

The advent of techniques such as microarrays and high-throughput sequencing has revolutionized our ability to examine messenger rna (mrna) expression within the respiratory system. Importantly, these approaches have also uncovered the widespread expression of "noncoding rnas," including micrornas and long noncoding rnas, which impact biologic responses through the regulation of mrna transcription and/or translation. To date, most studies of the role of noncoding rnas have focused on micrornas, which regulate mrna translation via the rna interference pathway. These studies have shown changes in microrna expression in cells and tissues derived from patients with asthma, pulmonary fibrosis, cystic fibrosis, COPD, and non-small cell lung cancer. Although the evidence is currently limited, we review the work that has been carried out in cell and animal models that has identified the function and mechanism of action of a small number of these micrornas in disease etiology. In addition to micrornas, we assess the emerging evidence that long noncoding rnas regulate respiratory phenotype. Because these investigations into long noncoding rnas were performed almost exclusively in non-small cell lung cancer, future work will need to extend these into other respiratory diseases and to analyze how micrornas and long noncoding rnas interact to regulate mrna expression. From a clinical perspective, the targeting of noncoding rnas as a novel therapeutic approach will require a deeper understanding of their function and mechanism of action. However, in the short term, changes in mirna and long noncoding rna expression are likely to be of use as biomarkers for disease stratification and/or assessment of drug action.

关键词： CF cystic fibrosis CFTR cystic fibrosis transmembrane conductance regulator HASM human airway smooth muscle IPF idiopathic pulmonary fibrosis lncrna long noncoding rna MALAT1 metastasis associated in lung adenocarcinoma transcript 1 MEG3 maternally expressed gene 3 mirna microrna mrna messenger rna ncrna noncoding rna NSCLC non-small cell lung cancer SCAL1 smoke and cancer-associated long noncoding rna-1 TGF transforming growth factor

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Exercise Mediates noncoding rnas in Cardiovascular Diseases: Pathophysiological Roles and Clinical Application

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EXPERT REVIEWS IN MOLECULAR MEDICINE 2024年 27卷 e2-e2页

作者： Wu, Changyong Chen, Xiaocui Yang, Lu Sun, Huang Bao, Suli Li, Haojie Zheng, Lihui Zeng, Huiling Li, Ruijie Peng, Yunzhu Kunming Med Univ Dept Cardiol Affiliated Hosp 1 Kunming Yunnan Peoples R China Panzhihua Univ Dept Gastroenterol Affiliated Hosp Panzhihua Sichuan Peoples R China

Exercise-based cardiac rehabilitation is effective in improving cardiovascular disease risk factor management, cardiopulmonary function, and quality of life. However, the precise mechanisms underlying exercise-induced cardioprotection remain elusive. Recent studies have shed light on the beneficial functions of noncoding rnas in either exercise or illness models, but only a limited number of noncoding rnas have been studied in both contexts. Hence, the present study aimed to elucidate the pathophysiological implications and molecular mechanisms underlying the association among exercise, noncoding rnas, and cardiovascular diseases. Additionally, the present study analysed the most effective and personalized exercise prescription, serving as a valuable reference for guiding the clinical implementation of cardiac rehabilitation in patients with cardiovascular diseases.

关键词： cardiovascular disease cardiac fibrosis cardiac rehabilitation exercise molecular mechanism noncoding rna

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