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Non-coding rnas in vascular remodeling and restenosis

VASCULAR PHARMACOLOGY 2019年 114卷 49-63页

作者： Indolfi, Ciro Iaconetti, Claudio Gareri, Clarice Polimeni, Alberto De Rosa, Salvatore Magna Graecia Univ Catanzaro Dept Med & Surg Sci Div Cardiol Catanzaro Italy Magna Graecia Univ Catanzaro CNR IFC URT Catanzaro Italy

Vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) are crucial in vascular remodeling. They exert pivotal roles in the development and progression of atherosclerosis, vascular response to injury, and restenosis after transcatheter angioplasty. As a witness of their importance in the cardiovascular system, a large body of evidence has accumulated about the role played by micro rnas (mirna) in modulating both VSMCs and ECs. More recently, a growing number of long noncoding rna (lncrnas) came beneath the spotlights in this research field. Several mechanisms have been revealed by which lncrnas are able to exert a relevant biological impact on vascular remodeling. The aim of this review is to provide an integrated summary of ncrnas that exert a relevant biological function in VSMCs and ECs of the vascular wall, with emphasis on the available clinical evidence of the potential usefulness of these molecules as circulating biomarkers of in-stent restenosis.

关键词： Restenosis noncoding rna Vascular remodeling micrornas

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Mechanisms by Which Small rnas Affect Bacterial Activity

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JOUrnaL OF DENTAL RESEARCH 2019年第12期98卷 1315-1323页

作者： Lei, L. Yang, Y. Wu, S. Ma, X. Mao, M. Hu, T. Sichuan Univ West China Hosp Stomatol Dept Prevent Dent State Key Lab Oral Dis 143rd SectRenmin South Rd Chengdu 610041 Sichuan Peoples R China Cent South Univ State Key Lab Powder Met Changsha Hunan Peoples R China Sichuan Univ West China Hosp Chengdu Sichuan Peoples R China Chinese Acad Sci Chengdu Inst Biol Chengdu Sichuan Peoples R China Shanghai Jiao Tong Univ Peoples Hosp 9 Sch Med 639 Zhizao Ju Rd Shanghai 200240 Peoples R China

The oral cavity contains a distinct habitat that supports diverse bacterial flora. Recent observations have provided additional evidence that srnas are key regulators of bacterial physiology and pathogenesis. These srnas have been divided into 5 functional groups: cis-encoded rnas, trans-encoded rnas, rna regulators of protein activity, bacterial CRISPR (clustered regularly interspaced short palindromic repeat) rnas, and a novel category of mirna-size small rnas (msrnas). In this review, we discuss a critical group of key commensal and opportunistic oral pathogens. In general, supragingival bacterial srnas function synergistically to fine-tune the regulation of cellular processes and stress responses in adaptation to environmental changes. Particularly in the cariogenic bacteria Streptococcus mutans, both the antisense vicR rna and msrna1657 can impede the metabolism of bacterial exopolysaccharides, prevent biofilm formation, and suppress its cariogenicity. In Enterococcus faecalis, selected srnas control the expression of proteins involved in diverse cellular processes and stress responses. In subgingival plaques, srnas from periodontal pathogens can function as novel bacterial signaling molecules that mediate bacterial-human interactions in periodontal homeostasis. In Porphyromonas gingivalis, the expression profiles of putative srna101 and srna42 were found to respond to hemin availability after hemin starvation. Regarding Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), a major periodontal pathogen associated with aggressive periodontitis, the predicted srnas interact with several virulence genes, including those encoding leukotoxin and cytolethal distending toxin. Furthermore, in clinical isolates, these associated rnas could be explored not only as potential biomarkers for oral disease monitoring but also as alternative types of regulators for drug design. Thus, this emerging subspecialty of bacterial regulatory rnas cou

关键词： biofilm dental plaque noncoding rna pathogenicity polysaccharides regulation

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miR-10a-5p is increased in atopic dermatitis and has capacity to inhibit keratinocyte proliferation

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ALLERGY 2019年第11期74卷 2146-2156页

作者： Vaher, Helen Runnel, Toomas Urgard, Egon Aab, Alar Badosa, Gemma Carreras Maslovskaja, Julia Abram, Kristi Raam, Liisi Kaldvee, Bret Annilo, Tarmo Tkaczyk, Eric R. Maimets, Toivo Akdis, Cezmi A. Kingo, Kulli Rebane, Ana Univ Tartu Inst Biomed & Translat Med Ravila 14B EE-50414 Tartu Estonia Univ Tartu Inst Mol & Cellular Biol Tartu Estonia Univ Tartu Tartu Univ Hosp Dept Dermatol & Venereol Dermatol Clin Tartu Estonia Univ Tartu Estonian Genome Ctr Inst Genom Tartu Estonia Dept Vet Affairs Nashville TN USA Vanderbilt Univ Med Ctr Nashville TN USA Univ Zurich Swiss Inst Allergy & Asthma Res SIAF Davos Switzerland

Background miR-10a-5p has been shown to regulate cancer cell proliferation and invasiveness and endothelial cell inflammatory responses. The function of miR-10a-5p in the skin has not been previously studied. The aim of the current study was to examine miR-10a-5p expression, regulation, and function in keratinocytes (KCs) in association with atopic dermatitis (AD). Methods The expression of miR-10a-5p and its target genes was analyzed using RT-qPCR, mrna array analysis, in situ hybridization, and immunofluorescence. The transfection of mirna mimics, cell cycle distribution analysis, and luciferase assays was used to study miR-10a-5p functions in human primary KCs. Results miR-10a-5p was found to be upregulated in lesional skin from patients with AD and in proliferating KCs. Array and pathway analysis of IL-1 beta-stimulated KCs revealed that miR-10a-5p inhibited many genes that affect cell cycle progression and only a few inflammation-related genes. Accordingly, fewer cells in S-phase and reduced proliferation were detected as characteristics of miR-10a-5p-transfected KCs. The influence of miR-10a-5p on cell proliferation was also evident in KCs induced by AD-related cytokines, including IL-4, IL-17, and IL-1 beta, as measured by the capacity to strongly suppress the expression of the proliferation marker Ki-67. Among AD-related putative direct target genes, we verified hyaluronan synthase 3, a damage-associated positive regulator of KC migration and proliferation, as a direct target of miR-10a-5p. Conclusions miR-10a-5p inhibits KC proliferation and directly targets hyaluronan synthase 3 and thereby may modulate AD-associated processes in the skin.

关键词： allergy atopic eczema cell cycle hyaluronic acid noncoding rna

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Validation of Circular rnas Using RT-qPCR After Effective Removal of Linear rnas by Ribonuclease R

CURRENT PROTOCOLS

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CURRENT PROTOCOLS 2021年第7期1卷 e181页

作者： Vromman, Marieke Yigit, Nurten Verniers, Kimberly Lefever, Steve Vandesompele, Jo Volders, Pieter-Jan Univ Ghent Dept Biomol Med Ctr Med Genet Ghent Ghent Belgium Canc Res Inst Ghent OncoRNALab Ghent Belgium VIB VIB UGent Ctr Med Biotechnol Ghent Belgium

Circular rnas (circrnas) are a class of endogenous noncoding rnas that have been shown to play a role in normal development, homeostasis, and disease, including cancer. Circrnas are formed through a process called back-splicing, which results in a covalently closed loop with a nonlinear back-spliced junction (BSJ). In general, circrna BSJs are predicted in rna sequencing data using one of numerous circrna detection algorithms. Selected circrnas are then typically validated using an orthogonal method such as reverse transcription quantitative PCR (RT-qPCR) with circrna-specific primers. However, linear transcripts originating from endogenous trans-splicing can lead to false-positive signals both in rna sequencing and in RT-qPCR experiments. Therefore, it is essential to perform the RT-qPCR validation step only after linear rnas have been degraded using an exonuclease such as ribonuclease R (rnase R). Several rnase R protocols are available for circrna detection using rna sequencing or RT-qPCR. These protocols-which vary in enzyme concentration, rna input amount, incubation times, and cleanup steps-typically lack a detailed validated standard protocol and fail to provide a range of conditions that deliver accurate results. As such, some protocols use rnase R concentrations that are too high, resulting in partial degradation of the target circrnas. Here, we describe an optimized workflow for circrna validation, combining rnase R treatment and RT-qPCR. First, we outline the steps for circrna primer design and qPCR assay validation. Then, we describe rnase R treatment of total rna and, importantly, a subsequent essential buffer cleanup step. Lastly, we outline the steps to perform the RT-qPCR and discuss the downstream data analyses. (c) 2021 Wiley Periodicals LLC.

关键词： circular rna noncoding rna primer design ribonuclease R RT-qPCR

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Introns: Good Day Junk Is Bad Day Treasure

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TRENDS IN GENETICS 2019年第12期35卷 923-934页

作者： Parenteau, Julie Abou Elela, Sherif Univ Sherbrooke Fac Med & Sci Sante Dept Microbiol & Infectiol Sherbrooke PQ J1E 4K8 Canada

Introns are ubiquitous in eukaryotic transcripts. They are often viewed as junk rna but the huge energetic burden of transcribing, removing, and degrading them suggests a significant evolutionary advantage. Ostensibly, an intron functions within the host pre-mrna to regulate its splicing, transport, and degradation. However, recent studies have revealed an entirely new class of trans-acting functions where the presence of intronic rna in the cell impacts the expression of other genes in trans. Here, we review possible new mechanisms of intron functions, with a focus on the role of yeast introns in regulating the cell growth response to starvation.

关键词： intron starvation nutrient sensing splicing regulation TOR pathway noncoding rna regulation of ribosome biogenesis

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Unraveling the epigenetic landscape of depression: focus on early life stress

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DIALOGUES IN CLINICAL NEUROSCIENCE 2019年第4期21卷 341-357页

作者： Torres-Berrio, Angelica Issler, Orna Parise, Eric M. Nestler, Eric J. Icahn Sch Med Mt Sinai Nash Family Dept Neurosci One Gustave L Levy PlBox 1065 New York NY 10029 USA Icahn Sch Med Mt Sinai Friedman Brain Inst One Gustave L Levy PlBox 1065 New York NY 10029 USA

Depression is a devastating psychiatric disorder caused by a combination of genetic predisposition and life events, mainly exposure to stress. Early life stress (ELS) in particular is known to "scar" the brain, leading to an increased susceptibility to developing depression later in life via epigenetic mechanisms. Epigenetic processes lead to changes in gene expression that are not due to changes in NA sequence, but achieved via modulation of chromatin modifications, NA methylation, and noncoding rnas. Here we review common epigenetic mechanisms including the enzymes that take part in reading, writing, and erasing specific epigenetic marks. We then describe recent developments in understanding how ELS leads to changes in the epigenome that are manifested in increased susceptibility to depression-like abnormalities in animal models. We conclude with highlighting the need for future studies that will potentially enable the utilisation of the understanding of epigenetic changes linked to ELS for the development of much-needed novel therapeutic strategies and biomarker discovery. (C) 2019, AICH - Servier Group.

关键词： chromatin remodeling histone modification DNA methylation noncoding rna early life stress

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Stable Intronic Sequence rnas (sisrnas): An Expanding Universe

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TRENDS IN BIOCHEMICAL SCIENCES 2019年第3期44卷 258-272页

作者： Chan, Seow Neng Pek, Jun Wei Natl Univ Singapore Temasek Life Sci Lab 1 Res Link Singapore 117604 Singapore Natl Univ Singapore Dept Biol Sci 14 Sci Dr Singapore 117543 Singapore

Intronic sequences are often regarded as 'nonsense' transcripts that are rapidly degraded. We highlight here recent studies on intronic sequences that play regulatory roles as long noncoding rnas (Incrnas) which are classified as sisrnas. Interestingly, sisrnas come in different forms and are produced via a variety of ways. They regulate genes at the DNA, rna, and protein levels, and frequently engage in autoregulatory feedback loops to ensure cellular homeostasis under normal and stress conditions. Future directions, evolutionary insights, and potential implications of dysregulated sisrnas are also discussed, especially in relation to human pathogenesis.

关键词： sisrna noncoding rna lariat intron transcription regulation homeostasis feedback

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Identification and integrated analysis of key differentially expressed circular rnas in ER-positive subtype breast cancer

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EPIGENOMICS 2019年第3期11卷 297-321页

作者： Yuan, Chenwei Zhou, Liheng Zhang, Lei Yin, Kai Peng, Jing Sha, Rui Zhang, Shan Xu, Yaqian Sheng, Xiaonan Wang, Yaohui Lin, Yanping Xu, Shuguang Yin, Wenjin Lu, Jinsong Shanghai Jiao Tong Univ Dept Breast Surg Renji Hosp Sch Med Shanghai 200127 Peoples R China

Aim: To systematically profile and characterize the circular rna (circrna) expression pattern in estrogen receptor (ER)-positive breast cancer (BC). Materials & methods: Circrna expression profile was performed in ER-positive BC and adjacent nontumor tissues. The differentially expressed circrnas (DECs) was analyzed by bioinformatics. The analysis findings were validated by quantitative real-time PCR. Results: In total, 3653 DECs were detected in our ER-positive BC compared with the control. Bioinformatics analysis showed that some pathways related to cancer, especially BC, were significantly enriched. Additionally, hsa_circ_0087378 was validated to be downregulated in ER-positive BC and the hsa_circ_0087378-miR-1260b-SFRP1 axis was proposed to be a key regulatory pathway. Conclusion: This study revealed the general expression characteristics of specific DECs in ER-positive BC and hsa_circ_0087378 might be a promising candidate target.

关键词： bioinformatics breast cancer circular rna hsa_circ_0087378 microarray mirna miR-1260b noncoding rna SFRP1 tumorigenesis

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Expanded Expression Landscape and Prioritization of Circular rnas in Mammals

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CELL REPORTS 2019年第12期26卷 3444-+页

作者： Ji, Peifeng Wu, Wanying Chen, Shuai Zheng, Yi Zhou, Lin Zhang, Jinyang Cheng, Hao Yan, Jin Zhang, Shaogeng Yang, Penghui Zhao, Fangqing Chinese Acad Sci Beijing Inst Life Sci Computat Genom Lab Beijing 100101 Peoples R China Univ Chinese Acad Sci Beijing 100049 Peoples R China Beijing 302 Hosp Beijing 100039 Peoples R China Chinese Acad Sci Ctr Excellence Anim Evolut & Genet Kunming 650223 Yunnan Peoples R China

Circular rnas (circrnas) are emerging as essential regulators of various biological and disease processes. To comprehensively understand the diversity of circrnas and prioritize their importance, we present a large-scale study of circrna repertoires from multiple tissues from human, macaque, and mouse. We discovered totals of 104,388, 96,675, and 82,321 circrnas from the three species, respectively, with an average of 72.6% being successfully assembled into full-length transcripts for each species. Using these full-length circrnas, we identified thousands of evolutionarily conserved circrnas that were valuable for functional screening and prioritization. By constructing both species-specific and conserved gene co-expression networks, we inferred circrna functions on a global scale and prioritized promising functional candidates. To illustrate how well-established prior knowledge facilitates to screen functional candidates, we used the circrna co-expression networks to prioritize circrnas that may be involved in liver tumorigenesis and experimentally validated their functions.

关键词： circular rna circrna co-expression network functional prioritization noncoding rna rna-binding protein transcriptome

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Epigenetics: the missing link between genes and psychiatric disorders?

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DIALOGUES IN CLINICAL NEUROSCIENCE 2019年第4期21卷 337-338页

作者： Thibaut, Florence Univ Hosp Cochin Site Tarnier Paris France Paris Univ Fac Med Paris Descartes INSERM Inst Psychiat & NeurosciU1266 Paris France

Most studies describing epigenetic modifications have focused on NA methylation, but fewer studies have focused on histone modifications and noncoding NAs. Chromatin architecture and CCCTC-binding factor represent important noncoding regulatory elements that warrant further investigation in order to improve our understanding of the genomic basis of complex diseases such as psychiatric disorders. (C) 2019, AICH - Servier Group

关键词： epigenetics histones DNA methylation noncoding rna CTCF

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