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Sex Differences and Estrous Cycle Changes in Synaptic Plasticity-related microrna in the Rat Medial Amygdala

NEUROSCIENCE 2018年第0期379卷 405-414页

作者： Hirsch, Mauro Mozael Brusco, Janaina Vaccaro, Tamara Margis, Rogerio Moreira, Jorge E. Gottfried, Carmem Rasia-Filho, Alberto A. Univ Fed Rio Grande do Sul Dept Biochem Res Grp Neuroglial Plast BR-90035003 Porto Alegre RS Brazil INCT NIM CNPq Oswaldo Cruz Fdn Natl Inst Sci & Technol Neuroimmunomodulat Rio De Janeiro Brazil Univ Sao Paulo Ribeirao Preto Sch Med Dept Pathol & Forens Med BR-14049900 Ribeirao Preto SP Brazil Univ Sao Paulo Ribeirao Preto Sch Med Dept Neurol Neurosci & Behav BR-14049900 Ribeirao Preto SP Brazil Fed Univ Rio Grande do Sul UFRGS Ctr Biotechnol Porto Alegre RS Brazil Fed Univ Rio Grande do Sul UFRGS Lab Genomes & Plant Populat PPGBCM Porto Alegre RS Brazil Fed Univ Hlth Sci Dept Basic Sci Physiol BR-90050170 Porto Alegre RS Brazil

The posterodorsal medial amygdala (MePD) is a sex steroid-sensitive and sexually dimorphic subcortical area that dynamically modulates social behaviors in rats. As different microrna (mirna) can act as post-transcriptional regulators of synaptic processing, we addressed changes that occur in mirna expression in the MePD of males and females along the estrous cycle. The expression of miR25-3p, miR132-3p, miR138-5p, miR181a-5p, miR195-5p, and miR199a-5p, involved in neuronal cytoskeleton remodeling and synaptic plasticity, were evaluated by RT-qPCR. We found that the expression of miR138-5p was higher in males than in females along the different phases of the estrous cycle. Males also showed higher levels of miR-181a when compared to females in diestrus and estrus. On the other hand, when compared to females in proestrus, males presented lower levels of miR132-3p and miR199a-5p. The expression of miR25-3p was higher in diestrus females than in proestrus females. In addition, diestrus females showed higher values of miR25-3p, miR181a-5p, and miR1955p when compared to estrus females. These mirna expression profiles indicate a variable and fine-tuned protein regulation in the adult MePD. It is likely that these mirna can be involved in structural and functional synaptic features and plasticity characteristic of males and cycling females and for the MePD regulation of mammalian reproduction. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

关键词： extended amygdala neural plasticity sexual dimorphism estrous cycle noncoding rna

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The Impact of Air Pollution on Our Epigenome: How Far Is the Evidence? (A Systematic Review)

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CURRENT ENVIRONMENTAL HEALTH REPORTS 2018年第4期5卷 544-578页

作者： Alfano, Rossella Herceg, Zdenko Nawrot, Tim S. Chadeau-Hyam, Marc Ghantous, Akram Plusquin, Michelle Hasselt Univ Ctr Environm Sci Hasselt Belgium Int Agcy Res Canc IARC Epigenet Grp 150 Cours Albert Thomas F-69008 Lyon France Leuven Univ Environm & Hlth Unit Leuven Belgium Imperial Coll London Sch Publ Hlth Dept Epidemiol & Biostat London England

Purpose of Review This systematic review evaluated existing evidence linking air pollution exposure in humans to major epigenetic mechanisms: DNA methylation, micrornas, long noncoding rnas, and chromatin regulation. Recent Findings Eighty-two manuscripts were eligible, most of which were observational (85%), conducted in adults (66%) and based on DNA methylation (79%). Summary Most observational studies, except panel, demonstrated modest effects of air pollution on the methylome. Panel and experimental studies revealed a relatively large number of significant methylome alterations, though based on smaller sample sizes. Particulate matter levels were positively associated in several studies with global or LINE-1 hypomethylation, a hallmark of several diseases, and with decondensed chromatin structure. Several air pollution species altered the DNA methylation clock, inducing accelerated biological aging. The causal nature of identified associations is not clear, however, especially that most originate from countries with low air pollution levels. Existing evidence, gaps, and perspectives are highlighted herein.

关键词： Air pollution Epigenetics DNA methylation Micrornas noncoding rna Chromatin

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Biomaterial Cues Regulate Epigenetic State and Cell Functions-A Systematic Review

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TISSUE ENGINEERING PART B-REVIEWS 2018年第2期24卷 112-132页

作者： Lv, Longwei Tang, Yiman Zhang, Ping Liu, Yunsong Bai, Xiangsong Zhou, Yongsheng Peking Univ Dept Prosthodont Sch & Hosp Stomatol 22 Zhongguancun Ave South Beijing 100081 Peoples R China Beijing Key Lab Digital Stomatol Natl Engn Lab Digital & Mat Technol Stomatol Beijing Peoples R China

Biomaterial cues can act as potent regulators of cell niche and microenvironment. Epigenetic regulation plays an important role in cell functions, including proliferation, differentiation, and reprogramming. It is now well appreciated that biomaterials can alter epigenetic states of cells. In this study, we systematically reviewed the underlying epigenetic mechanisms of how different biomaterial cues, including material chemistry, topography, elasticity, and mechanical stimulus, influence cell functions, such as nuclear deformation, cell proliferation, differentiation, and reprogramming, to summarize the differences and similarities among each biomaterial cues and their mechanisms, and to find common and unique properties of different biomaterial cues. Moreover, this work aims to establish a mechanogenomic map facilitating highly functionalized biomaterial design, and renders new thoughts of epigenetic regulation in controlling cell fates in disease treatment and regenerative medicine.

关键词： biomaterial cues epigenetics cell behaviors chromatin remodeling noncoding rna

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Liquid biopsies for management of pancreatic cancer

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TRANSLATIONAL RESEARCH 2018年 201卷 98-127页

作者： Samandari, Mohamadmahdi Julia, Maria Gil Rice, Alistair Chronopoulos, Antonios Hernandez, Armando E. Del Rio Univ Tehran Coll Engn Sch Mech Engn North Kargar St Tehran 14395515 Iran Imperial Coll London Dept Bioengn Cellular & Mol Biomech Lab London SW7 2AZ England

Pancreatic cancer is one of the main causes of cancer-related deaths worldwide. It is asymptomatic at an early stage, and most diagnosis occurs when the disease is already at a late stage, by which time the tumor is nonresectable. In order to increase the overall survival of patients with pancreatic cancer, as well as to decrease the cancer burden, it is necessary to perform early diagnosis, prognosis stratifications and cancer monitoring using accurate, minimally invasive, and cost-effective methods. Liquid biopsies seek to detect tumor-associated biomarkers in a variety of extractable body fluids and can help to monitor treatment response and disease progression, and even predict patient outcome. In patients with pancreatic cancer, tumor-derived materials, primarily circulating tumor DNA, circulating tumor cells and exosomes, are being studied for inclusion in the management of the disease. This review focuses on describing the biology of these biomarkers, methods for their enrichment and detection, as well as their potential for clinical application. Moreover, we discuss the future direction of liquid biopsies and introduce how they can be exploited toward point of care personalized medicine for the management of pancreatic cancer.

关键词： AUC area under the curve CA19-9 carbohydrate antigen 19-9 CAF cancer associated fibroblast CD cluster of differentiation CEA carcinoembryonic antigen CEP8 chromosome enumeration probe 8 cfDNA cell free DNA cfNA cell-free nucleic acid CK cytokeratin CTC circulating tumor cell ctDNA circulating tumor DNA CTM circulating tumor microemboli dPCR digital PCR ECM extracellular matrix EDTA ethylenediaminetetraacetic acid EMT epithelial-to-mesenchymal transition EpCAM epithelial cell adhesion molecule FISH fluorescence in situ hybridization mirna microrna mrna messenger rna ncrna noncoding rna NGS next generation sequencing PCR polymerase chain reaction PDAC pancreatic ductal adenocarcinoma PSC pancreatic stellate cell WGS whole genome sequencing

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Lncrnas and miRs as epigenetic signatures in diabetic cardiac fibrosis: new advances and perspectives

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ENDOCRINE 2018年第2期62卷 281-291页

作者： Tao, Hui Song, Zheng-Yu Ding, Xuan-Sheng Yang, Jing-Jing Shi, Kai-Hu Li, Jun China Pharmaceut Univ Sch Basic Med Sci & Clin Pharm Nanjing 210009 Jiangsu Peoples R China Anhui Med Univ Hosp 2 Dept Cardiothorac Surg Hefei 230601 Anhui Peoples R China Anhui Med Univ Hosp 2 Dept Pharmacol Hefei 230601 Anhui Peoples R China Nanjing Univ Chinese Med Affiliated Hosp Integrated Tradit Chinese & Weste Dept Cardiothorac Surg Nanjing 210028 Jiangsu Peoples R China Anhui Med Univ Sch Pharm Hefei 230032 Anhui Peoples R China

PurposeDiabetic cardiomyopathy (DCM) is a serious cardiac complication of diabetes, which further lead to heartfailure. It is known that diabetes-induced cardiac fibrosis is a key pathogenic factor contributing topathological changes in DCM. However, pathogenetic mechanisms underlying diabetes cardiac fibrosis arestill elusive. Recent studies have indicated that noncoding rnas (ncrnas) play a key role in diabetescardiac fibrosis. The increasing complexity of epigenetic regulator poses great challenges to ourconventional conceptions regarding how ncrnas regulate diabetes cardiac *** searched PubMed, Web of Science, and Scopus for manuscripts published prior to April 2018 using keywords "Diabetic cardiomyopathy" AND " diabetes cardiac fibrosis " OR " noncoding rnas " OR " longnoncoding rnas " OR " micrornas " OR "epigenetic". Manuscripts were collated, studied and carriedforward for discussion where *** on the view that during diabetic cardiac fibrosis, ncrnas are able to regulate diabetic cardiac fibrosisby targeting genes involved in epigenetic pathways. Many studies have focused on ncrnas, an epigeneticregulator deregulating protein-coding genes in diabetic cardiac fibrosis, to identify potential therapeutictargets. Recent advances and new perspectives have found that long noncoding rnas and micrornas,exert their own effects on the progression of diabetic cardiac *** firstly examine the growing role of ncrnas characteristics and ncrnas-regulated genes involved indiabetic cardiac fibrosis. Then, we provide several possible therapeutic strategies and highlight the potentialof molecular mechanisms in which targeting epigenetic regulators are considered as an effective means of treating diabetic cardiac fibrosis.

关键词： Diabetic cardiac fibrosis Epigenetic noncoding rna Long noncoding rna Micrornas

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Subgenomic flaviviral rnas: What do we know after the first decade of research

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ANTIVIRAL RESEARCH 2018年第0期159卷 13-25页

作者： Slonchak, Andrii Khromykh, Alexander A. Univ Queensland Sch Chem & Mol Biosci Australian Infect Dis Ctr St Lucia Qld 4072 Australia

The common feature of flaviviral infection is the accumulation of abundant virus-derived noncoding rna, named flaviviral subgenomic rna (sfrna) in infected cells. This rna represents a product of incomplete degradation of viral genomic rna by the cellular 5'-3' exoribonuclease XRN1 that stalls at the conserved highly structured elements in the 3' untranslated region (UTR). This mechanism of sfrna generation was discovered a decade ago and since then sfrna has been a focus of intense research. The ability of flaviviruses to produce sfrna was shown to be evolutionary conserved in all members of Flavivirus genus. Mutations in the 3'UTR that affect production of sfrnas and their interactions with host factors showed that sfrnas are responsible for viral pathogenicity, host adaptation, and emergence of new pathogenic strains. rna structural elements required for XRN1 stalling have been elucidated and the role of sfrnas in inhibiting host antiviral responses in arthropod and vertebrate hosts has been demonstrated. Some molecular mechanisms determining these properties of sfrna have been recently characterized, while other aspects of sfrna functions remain an open avenue for future research. In this review we summarise the current state of knowledge on the mechanisms of generation and functional roles of sfrnas in the life cycle of flaviviruses and highlight the gaps in our knowledge to be addressed in the future.

关键词： Flavivirus sfrna noncoding rna Subgenomic flaviviral rna XRN-1 resistance

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cernas in plants: computational approaches and associated challenges for target mimic research

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BRIEFINGS IN BIOINFORMATICS 2018年第6期19卷 1273-1289页

作者： Paschoal, Alexandre Rossi Lozada-Chavez, Irma Domingues, Douglas Silva Stadler, Peter F. Fed Univ Technol Parana UTFPR Cornelio Procopio Parana Brazil Univ Leipzig Interdisciplinary Ctr Bioinformat Leipzig Germany Mexican Soc Astrobiol SOMA Mexico City DF Mexico Sao Paulo State Univ UNESP Inst Biosci Dept Bot Rio Claro Brazil Univ Vienna Theoret Chem Vienna Austria Santa Fe Inst Santa Fe NM 87501 USA Max Planck Gesell Munich Germany Austrian Acad Sci Vienna Austria

The competing endogenous rna hypothesis has gained increasing attention as a potential global regulatory mechanism of micrornas (mirnas), and as a powerful tool to predict the function of many noncoding rnas, including mirnas themselves. Most studies have been focused on animals, although target mimic (TMs) discovery as well as important computational and experimental advances has been developed in plants over the past decade. Thus, our contribution summarizes recent progresses in computational approaches for research of mirna: TM interactions. We divided this article in three main contributions. First, a general overview of research on TMs in plants is presented with practical descriptions of the available literature, tools, data, databases and computational reports. Second, we describe a common protocol for the computational and experimental analyses of TM. Third, we provide a bioinformatics approach for the prediction of TM motifs potentially cross-targeting both members within the same or from different mirna families, based on the identification of consensus mirna-binding sites from known TMs across sequenced genomes, transcriptomes and known mirnas. This computational approach is promising because, in contrast to animals, mirna families in plants are large with identical or similar members, several of which are also highly conserved. From the three consensus TM motifs found with our approach: MIM166, MIM171 and MIM159/319, the last one has found strong support on the recent experimental work by Reichel and Millar [Specificity of plant microrna TMs: cross-targeting of mir159 and mir319. J Plant Physiol 2015;180: 45-8]. Finally, we stress the discussion on the major computational and associated experimental challenges that have to be faced in future cerna studies.

关键词： target mimics cerna consensus cerna motif computational method noncoding rna bioinformatics

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Profiles of differentially expressed circrnas in esophageal and breast cancer

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CANCER MANAGEMENT AND RESEARCH 2018年 10卷 2207-2221页

作者： Shi, Peiyi Sung, Jian He, Biyu Song, Huan Li, Zhongqi Kong, Weimin Wang, Jianping Wang, Jianming Xue, Hengchuan Nanjing Med Univ Sch Publ Hlth Dept Epidemiol 101 Longmian Ave Nanjing 211166 Jiangsu Peoples R China First Peoples Hosp Yancheng City Dept Thorac Surg Yancheng Peoples R China Peoples Hosp Yangzhong Dept Thorac Surg 235 Yangzi Middle Rd Yangzhong 212200 Peoples R China

Introduction: Circular rnas (circrnas) function as efficient microrna sponges with gene-regulatory potential and are promising cancer biomarkers. In this study, we used the Arraystar Human circrna Array to construct a genome-wide circrna profile of esophageal squamous cell cancer (ESCC) and breast cancer (BC). Patients and methods: Expression levels between cancer lesions and adjacent normal-appearing tissues were compared. We observed 469 upregulated circrnas and 275 downregulated circrnas in ESCC. Hsa_circrna_103670 was upregulated 20.3-fold, while hsa_circrna_030162 was downregulated 12.1-fold. For BC, 715 circrnas were upregulated, and 440 circrnas were downregulated. Hsa_circrna_005230 was upregulated 12.2-fold, while hsa_circrna_406225 was downregulated 12.4-fold. Results: When we set the criteria as fold change in expression >= 2 between cancer and adjacent normal-appearing tissue with a P-value <0.01, there were 22 common circrnas (11 upregulated and 11 downregulated) in relation to both ESCC and BC. Gene ontology and the Kyoto encyclopedia of genes and genomes analyses showed that these circrnas were involved in the tumorigenesis of human cancers. Conclusion: Our study revealed that circrnas are promising candidates as valuable biomarkers for ESCC and BC, although relevant research is still in its infancy and the functional role of specific circrnas in tumorigenesis is just starting to be elucidated.

关键词： circrna noncoding rna esophageal squamous cell carcinoma breast cancer biomarker

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Long noncoding rnas. Molecular switch and therapeutic target molecules of disease processes

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NEPHROLOGE 2017年第1期12卷 59-61页

作者： Lorenzen, J. M. Univ Spital Zurich Ramistr 100 CH-8091 Zurich Switzerland

Long noncoding rnas (lncrna) are regulatory rna species, which have recently come into the focus of scientific interest. Until now little was known about their mode of action, although according to many studies it was presumed that they exercise an important epigenetic function within cells under physiological conditions as well as in disease processes. This article presents some of these regulatory functions and the suggested classification due to the localization as well as the current functional classification of lncrnas. Several lncrnas have now been identified that are important within the framework of renal and cardiovascular diseases. On the basis of the most recent resarch results, this article demonstrates how novel therapeutic routes for these diseases can be pursued in the future using lncrna antagonists or viral constructs on overexpression.

关键词： noncoding rna Epigenetics Kidney diseases Cardiovascular diseases Therapeutics

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Pan-Cancer Analysis of lncrna Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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CELL REPORTS 2018年第1期23卷 297-+页

作者： Chiu, Hua-Sheng Somvanshi, Sonal Patel, Ektaben Chen, Ting-Wen Singh, Vivek P. Zorman, Barry Patil, Sagar L. Pan, Yinghong Chatterjee, Sujash S. Sood, Anil K. Gunaratne, Preethi H. Sumazin, Pavel Baylor Coll Med Texas Childrens Canc Ctr Houston TX 77030 USA Chang Gung Univ Bioinformat Ctr Mol Med Res Ctr Taoyuan Taiwan Baylor Coll Med Dept Surg Houston TX 77030 USA Univ Houston Dept Biol & Biochem Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Dept Gynecol Oncol & Reprod Med Div Surg Houston TX 77030 USA

Long noncoding rnas (lncrnas) are commonly dysregulated in tumors, but only a handful are known to play pathophysiological roles in cancer. We inferred lncrnas that dysregulate cancer pathways, oncogenes, and tumor suppressors (cancer genes) by modeling their effects on the activity of transcription factors, rna-binding proteins, and micrornas in 5,185 TCGA tumors and 1,019 ENCODE assays. Our predictions included hundreds of candidate onco- and tumor-suppressor lncrnas (cancer lncrnas) whose somatic alterations account for the dysregulation of dozens of cancer genes and pathways in each of 14 tumor contexts. To demonstrate proof of concept, we showed that perturbations targeting OIP5-AS1 (an inferred tumor suppressor) and TUG1 and WT1-AS (inferred onco- lncrnas) dysregulated cancer genes and altered proliferation of breast and gynecologic cancer cells. Our analysis indicates that, although most lncrnas are dysregulated in a tumor-specific manner, some, including OIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergistically dysregulate cancer pathways in multiple tumor contexts.

关键词： lncrna regulation modulation cancer gene pan-cancer noncoding rna microrna rna-binding proteins interactome

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