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Hfq reduces envelope stress by controlling expression of envelope-localized proteins and protein complexes in enteropathogenic Escherichia coli

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MOLECULAR MICROBIOLOGY 2014年第4期92卷 681-697页

作者： Vogt, Stefanie L. Raivio, Tracy L. Univ Alberta Dept Biol Sci Edmonton AB T6G 2E9 Canada

Gram-negative bacteria possess several envelope stress responses that detect and respond to damage to this critical cellular compartment. The sigma(E) envelope stress response senses the misfolding of outer membrane proteins (OMPs), while the Cpx two-component system is believed to detect the misfolding of periplasmic and inner membrane proteins. Recent studies in several Gram-negative organisms found that deletion of hfq, encoding a small rna chaperone protein, activates the sigma(E) envelope stress response. In this study, we assessed the effects of deleting hfq upon activity of the sigma(E) and Cpx responses in non-pathogenic and enteropathogenic (EPEC) strains of Escherichia coli. We found that the sigma(E) response was activated in hfq mutants of all *** strains tested, resulting from the misregulation of OMPs. The Cpx response was activated by loss of hfq in EPEC, but not in ***-12. Cpx pathway activation resulted in part from overexpression of the bundle-forming pilus (BFP) in EPEC hfq. We found that Hfq repressed expression of the BFP via PerA, a master regulator of virulence in EPEC. This study shows that Hfq has a more extensive role in regulating the expression of envelope proteins and horizontally acquired virulence genes in *** than previously recognized.

关键词： ESCHERICHIA coli GRAM-negative bacteria MEMBRANE proteins MOLECULAR chaperones non-coding rna VIRULENCE (Microbiology)

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Radiation-induced microrna: Discovery, Functional Analysis, and Cancer Radiotherapy

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JOUrnaL OF CELLULAR BIOCHEMISTRY 2014年第3期115卷 436-449页

作者： Chaudhry, M. Ahmad Univ Vermont Dept Med Lab & Radiat Sci Burlington VT 05405 USA

Micrornas (mirnas) are small non-protein coding rna that play an important role in gene regulation. These rna molecules function as post-transcriptional regulators. mirnas bind to complementary sequences on target messenger rna transcripts, usually resulting in translational repression or target mrna degradation and gene silencing. mirna are abundantly present in all human cells, target approximately 60% of all genes, and are able to repress hundreds of targets each. Since their discovery in 1993 mirna are emerging as important modulators in cellular pathways such as growth and proliferation, apoptosis, carcinogenesis, timing of cell-fate decision, and metabolic pathways. A large number of studies have examined the general and specific effects of mirnas perturbation in radiation-exposed cells. These studies include expression profiling of mirna, functional analysis, the role of specific mirnas in tumor radiosensitivity, and targeting mirna for improved cancer radiotherapy. Other studies have explored the involvement of mirna in radiobiological phenomenon like bystander effect. Emerging evidence is establishing that mirna are involved in regulating radiation-induced cellular processes, can be exploited to improve cancer radiation therapy, and could serve as biomarkers of human radiation exposure. J. Cell. Biochem. 115: 436-449, 2014. (c) 2013 Wiley Periodicals, Inc.

关键词： RADIATION EFFECTS non-coding rna MICROrna RADIATION SENSITIVITY BIOMARKERS

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Candidate lncrna-microrna-mrna networks in predicting non-small cell lung cancer and related prognosis analysis

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JOUrnaL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 2020年第4期146卷 883-896页

作者： Li, Sixuan Cui, Zhigang Zhao, Yuxin Ma, Shuwen Sun, Yinghui Li, Hang Gao, Min Li, Na Wang, Ying Tong, Lianwei Song, Mingyang Yin, Zhihua China Med Univ Shenyang 110122 Peoples R China China Med Univ Sch Publ Hlth Dept Epidemiol Shenyang 110122 Peoples R China Univ Liaoning Prov Key Lab Canc Etiol & Intervent Shenyang North New Area 77 Puhe Rd Shenyang 110122 Peoples R China

Purpose The role of non-coding rna, once thought to be dark matter, is increasingly prominent in cancer. Our article explores the effect of non-coding rna in lung adenocarcinoma and lung squamous cell carcinoma by mining TCGA public database. Methods Download the data by applying the official TCGA software. The data were analyzed by R data analysis packages, 'edgeR', 'gplots' and 'survival'. We better illustrate the potential networks of lung cancer genes by constructing cernas, using Cytoscape software. Results We obtained genes which were differentially expressed in lung adenocarcinoma and lung squamous cell carcinoma analysis. Within these differentially expressed genes, we also conducted a survival analysis to find differentially expressed genes associated with prognosis in both lung adenocarcinoma and lung squamous cell carcinoma. Based on genes differentially expressed of both lung adenocarcinoma and lung squamous cell carcinoma, we constructed a cerna network to illustrate the mechanism of lung adenocarcinoma and lung squamous cell carcinoma. Our study analyzed genes which were differentially expressed in lung adenocarcinoma and lung squamous cell carcinoma using the TCGA database. Conclusion Based on this, the prognosis in both lung squamous cell carcinoma and lung adenocarcinoma was analyzed. We have also constructed a cerna network to provide a basis for the study of cerna in lung adenocarcinoma and lung squamous cell carcinoma.

关键词： TCGA non-coding rna Lung cancer Prognosis cerna

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Long noncoding rna PEG10 regulates proliferation and invasion of esophageal cancer cells

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CANCER GENE THERAPY 2015年第3期22卷 138-144页

作者： Zang, W. Wang, T. Huang, J. Li, M. Wang, Y. Du, Y. Chen, X. Zhao, G. Zhengzhou Univ Coll Basic Med Sci Zhengzhou 450001 Henan Province Peoples R China Henan Univ TCM Affiliated Hosp 1 Dept Hematotumor Zhengzhou Peoples R China

Long chain noncoding rnas (Lncrnas), a class of noncoding rna nucleotides longer than 200 bp, have important roles in a variety of biological processes. Accumulating evidence has confirmed the involvement of Lncrnas in cancer initiation, development and progression. We investigated the expression of Lncrna PEG10 in a cohort of esophageal carcinomas to assess its impact on esophageal cancer cell proliferation, apoptosis and invasion. Quantitaive reverse transcription polymerase chain reaction assays were used to quantify Lncrna PEG10 expression levels in 43 paired EC samples and adjacent non-neoplastic tissues. Cell growth, apoptosis and Transwell invasion assays were used to evaluate the effects of Lncrna PEG10 on esophageal cancer cells. Lncrna PEG10 was expressed at higher levels in esophageal cancer tissues than in adjacent non-neoplastic tissues (P < 0.05). This relatively high expression was significantly associated with the occurrence of lymph node metastases (P < 0.05). Apoptosis and migration rates were significantly decreased in two esophageal cancer cell lines (EC9706 and KYSE150) transfected with si-Lncrna PEG10 (P < 0.05). Downregulation of Lncrna PEG10 decreased the expression of PEG10 (P < 0.05). Our results indicated that Lncrna PEG10 is upregulated in esophageal cancer tissues, and its downregulation inhibits proliferation and invasion, and promotes apoptosis in esophageal cancer cells. Lncrna PEG10 may serve as a therapeutic agent in esophageal cancer.

关键词： ESOPHAGEAL cancer -- Treatment non-coding rna CELL proliferation CANCER invasiveness NUCLEOTIDES BIOACCUMULATION

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The multifaceted actions of the lncrna H19 in cardiovascular biology and diseases

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CLINICAL SCIENCE 2022年第15期136卷 1157-1178页

作者： Busscher, Denise Boon, Reinier A. Juni, Rio P. Vrije Univ Amsterdam Dept Physiol Amsterdam UMC Boelelaan 1117 Amsterdam Netherlands Amsterdam Cardiovasc Sci Microcirculat Amsterdam Netherlands Goethe Univ Frankfurt Main Inst Cardiovasc Regenerat Ctr Mol Med Frankfurt Germany German Ctr Cardiovasc Res DZHK Partner site Frankfurt Rhein Main Frankfurt Germany

Cardiovascular diseases are the leading cause of death and debility worldwide. Various molecular mechanisms have been studied to better understand the development and progression of cardiovascular pathologies with hope to eradicate these diseases. With the advancement of the sequencing technology, it is revealed that the majority of our genome is non-coding. A growing body of literature demonstrates the critical role of long non-coding rnas (lncrnas) as epigenetic regulators of gene expression. Lncrnas can regulate cellular biological processes through various distinct molecular mechanisms. The abundance of lncrnas in the cardiovascular system indicates their significance in cardiovascular physiology and pathology. Lncrna H19, in particular, is a highly evolutionarily conserved lncrna that is enriched in cardiac and vascular tissue, underlining its importance in maintaining homeostasis of the cardiovascular system. In this review, we discuss the versatile function of H19 in various types of cardiovascular diseases. We highlight the current literature on H19 in the cardiovascular system and demonstrate how dysregulation of H19 induces the development of cardiovascular pathophysiology.

关键词： cardiovascular disease cardiovascular physiology large intervening non-coding rna lncrna H19 non-coding rna

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Role of epigenomic mechanisms in the onset and management of insulin resistance

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REVIEWS IN ENDOCRINE & METABOLIC DISORDERS 2019年第1期20卷 89-102页

作者： Izquierdo, Andrea G. Crujeiras, Ana B. Complejo Hosp Univ Santiago CHUS SERGAS Inst Invest Sanitaria IDIS Epigen Endocrinol & Nutr Grp C Choupana S-N Santiago De Compostela 15706 Spain CIBER Fisiopatol Obesidad & Nutr CIBERobn Madrid Spain

The prevalence of insulin resistance (IR) is increasing rapidly worldwide and it is a relevant health problem because it is associated with several diseases, such as type 2 diabetes, cardiovascular disorders and cancer. Understanding the mechanisms involved in IR onset and progression will open new avenues for identifying biomarkers for preventing and treating IR and its co-diseases. Epigenetic mechanisms such as DNA methylation are important factors that mediate the environmental effect in the genome by regulating gene expression and consequently its effect on the phenotype and the development of disease. Taking into account that IR results from a complex interplay between genes and the environment and that epigenetic marks are reversible, disentangling the relationship between IR and epigenetics will provide new tools to improve the management and prevention of IR. Here, we review the current scientific evidence regarding the association between IR and epigenetic markers as mechanisms involved in IR development and potential management.

关键词： DNA methylation non-coding rna Glucose homeostasis Insulin sensitivity Type 2 diabetes Biomarkers

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Diagnostic and therapeutic potential of micrornas in neuropsychiatric disorders: Past, present, and future

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PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY 2017年 73卷 87-103页

作者： Alural, Begum Genc, Sermin Haggarty, Stephen J. Dokuz Eylul Univ Dept Neurosci Fac Med Izmir Turkey Dokuz Eylul Univ Izmir Biomed & Genome Ctr Izmir Turkey Massachusetts Gen Hosp Ctr Human Genet Res Boston MA 02114 USA Harvard Med Sch Massachusetts Gen Hosp Dept Neurol Chem Neurobiol Lab Boston MA 02114 USA Harvard Med Sch Massachusetts Gen Hosp Dept Psychiat Boston MA 02114 USA

Neuropsychiatric disorders are common health problems affecting approximately 1% of the population. Twin, adoption, and family studies have displayed a strong genetic component for many of these disorders;however, the underlying pathophysiological mechanisms and neural substrates remain largely unknown. Given the critical need for new diagnostic markers and disease-modifying treatments, expanding the focus of genomic studies of neuropsychiatric disorders to include the role of non-coding rnas (ncrnas) is of growing interest. Of known types of ncrnas, micrornas (mirnas) are 20-25-nucleotide, single-stranded, molecules that regulate gene expression through post-transcriptional mechanisms and have the potential to coordinately regulate complex regulatory networks. In this review, we summarize the current knowledge on mirna alteration/dysregulation in neuropsychiatric disorders, with a special emphasis on schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). With an eye toward the future, we also discuss the diagnostic and prognostic potential of mirnas for neuropsychiatric disorders in the context of personalized treatments and network medicine. (C) 2016 Elsevier Inc All tights reserved.

关键词： non-coding rna Mirna Schizophrenia Bipolar disorder Neuroplasticity

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Microrna-155 expression and function in AML: An evolving paradigm

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EXPERIMENTAL HEMATOLOGY 2018年 62卷 1-6页

作者： Narayan, Nisha Bracken, Cameron P. Ekert, Paul G. Murdoch Childrens Res Inst 50 Flemington Rd Parkville Vic 3052 Australia SA Pathol Ctr Canc Biol Adelaide SA 5000 Australia Univ South Australia Adelaide SA 5000 Australia

Acute myeloid leukemia (AML) arises when immature myeloid blast cells acquire multiple, recurrent genetic and epigenetic changes that result in dysregulated proliferation. Acute leukemia is the most common form of pediatric cancer, with AML accounting for similar to 20% of all leukemias in children. The genomic aberrations that drive AML inhibit myeloid differentiation and activate signal transduction pathways that drive proliferation. Micrornas, a class of small (similar to 22 nucleotide) noncoding rnas that posttranscriptionally suppress the expression of specifically targeted transcripts, are also frequently dysregulated in AML, which may prove useful for the purposes of disease classification, prognosis, and future therapeutic approaches. Microrna expression profiles are associated with patient prognosis and responses to standard chemotherapy, including predicting therapy resistance in AML. miR-155 is the primary focus of this review because it has been repeatedly associated with poorer survival across multiple cohorts of adult and pediatric AML. We discuss some novel features of miR-155 expression in AML, in particular how the levels of expression can critically influence function. Understanding the role of micrornas in AML and the ways in which microrna expression influences AML biology is one means to develop novel and more targeted therapies. (C) 2018 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

关键词： MICROrna ACUTE myeloid leukemia EPIGENETICS PEDIATRICS non-coding rna

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Molecular Crosstalking among noncoding rnas: A New Network Layer of Genome Regulation in Cancer

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INTErnaTIONAL JOUrnaL OF GENOMICS 2017年第1期2017卷 1-17页

作者： Ragusa, Marco Barbagallo, Cristina Brex, Duilia Caponnetto, Angela Cirnigliaro, Matilde Battaglia, Rosalia Barbagallo, Davide Di Pietro, Cinzia Purrello, Michele Univ Catania Dept BioMed Sci & Biotechnol Sect Biol & Genet G Sichel BioMol Genome & Complex Syst BioMed Unit BMGS Uni Catania Italy IRCCS Associaz Oasi Maria SS Inst Res Mental Retardat & Brain Aging Troina Enna Italy

Over the past few years, noncoding rnas (ncrnas) have been extensively studied because of the significant biological roles that they play in regulation of cellular mechanisms. ncrnas are associated to higher eukaryotes complexity;accordingly, their dysfunction results in pathological phenotypes, including cancer. To date, most research efforts have been mainly focused on how ncrnas could modulate the expression of protein-coding genes in pathological phenotypes. However, recent evidence has shown the existence of an unexpected interplay among ncrnas that strongly influences cancer development and progression. ncrnas can interact with and regulate each other through various molecular mechanisms generating a complex network including different species of rnas (e.g., mrnas, mirnas, lncrnas, and circrnas). Such a hidden network of rna-rna competitive interactions pervades and modulates the physiological functioning of canonical protein-coding pathways involved in proliferation, differentiation, and metastasis in cancer. Moreover, the pivotal role of ncrnas as keystones of network structural integrity makes them very attractive and promising targets for innovative rna-based therapeutics. In this review we will discuss: (1) the current knowledge on complex crosstalk among ncrnas, with a special focus on cancer;and (2) the main issues and criticisms concerning ncrnas targeting in therapeutics.

关键词： non-coding rna CROSS-talk (Biology) GENE expression PROTEIN expression GENETIC regulation MOLECULAR interactions CELL proliferation CELL differentiation

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Progress in cardiac research: from rebooting cardiac regeneration to a complete cell atlas of the heart

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CARDIOVASCULAR RESEARCH 2021年第10期117卷 2161-2174页

作者： Davidson, Sean M. Padro, Teresa Bollini, Sveva Vilahur, Gemma Duncker, Dirk J. Evans, Paul C. Guzik, Tomasz Hoefer, Imo E. Waltenberger, Johannes Wojta, Johann Weber, Christian UCL Hatter Cardiovasc Inst 67 Chenies Mews London WC1E 6HX England Hosp Santa Creu & St Pau IIB St Pau Inst Recerca Cardiovasc Program ICCC Barcelona Spain Inst Salud Carlos III ISCIII CIBER Enfermedades Cardiovasc CIBERCV Madrid Spain Univ Genoa Dept Expt Med DIMES Genoa Italy Erasmus MC Thoraxctr Dept Cardiol Div Expt Cardiol Rotterdam Netherlands Univ Sheffield Dept Infect Immun & Cardiovasc Dis Sheffield S Yorkshire England Univ Sheffield Insigneo Inst Sheffield S Yorkshire England Univ Glasgow British Heart Fdn Ctr Cardiovasc Res Inst Cardiovasc & Med Sci Glasgow Lanark Scotland Jagiellonian Univ Coll Med Dept Med Krakow Poland Univ Med Ctr Utrecht Cent Diagnost Lab Utrecht Netherlands Univ Munster Med Fac Dept Cardiovasc Med Munster Germany Med Univ Vienna Dept Internal Med 2 Vienna Austria Ludwig Maximilians Univ Munchen Inst Cardiovasc Prevent IPEK DZHK German Ctr Cardiovasc Res Partner Site Munich Heart Alliance Munich Germany Ludwig Maximilians Univ Munchen Inst Cardiovasc Prevent IPEK DZHK German Ctr Cardiovasc Res Munich Cluster Syst Neurol SyNergy Munich Germany Maastricht Univ Cardiovasc Res Inst Maastricht CARIM Dept Biochem Maastricht Netherlands

We review some of the important discoveries and advances made in basic and translational cardiac research in 2020. For example, in the field of myocardial infarction (MI), new aspects of autophagy and the importance of eosinophils were described. Novel approaches, such as a glycocalyx mimetic, were used to improve cardiac recovery following MI. The strategy of 3D bio-printing was shown to allow the fabrication of a chambered cardiac organoid. The benefit of combining tissue engineering with paracrine therapy to heal injured myocardium is discussed. We highlight the importance of cell-to-cell communication, in particular, the relevance of extracellular vesicles, such as exosomes, which transport proteins, lipids, non-coding rnas, and mrnas and actively contribute to angiogenesis and myocardial regeneration. In this rapidly growing field, new strategies were developed to stimulate the release of reparative exosomes in ischaemic myocardium. Single-cell sequencing technology is causing a revolution in the study of transcriptional expression at cellular resolution, revealing unanticipated heterogeneity within cardiomyocytes, pericytes and fibroblasts, and revealing a unique subpopulation of cardiac fibroblasts. Several studies demonstrated that exosome- and non-coding rna-mediated approaches can enhance human induced pluripotent stem cell (iPSC) viability and differentiation into mature cardiomyocytes. Important details of the mitochondrial Ca2+ uniporter and its relevance were elucidated. Novel aspects of cancer therapeutic-induced cardiotoxicity were described, such as the novel circular rna circITCH, which may lead to novel treatments. Finally, we provide some insights into the effects of SARS-CoV-2 on the heart. [GRAPHICS] .

关键词： Cardiac Myocardial infarction Myocardial injury Heart failure non-coding rna Cardiomyocyte division Induce pluripotent stem cells Cardiotoxicity Single-cell rna sequencing s COVID-19

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