Tesis sobre el tema "MicroRNA"
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Khoshnaw, Sarkawt Majeed Omar. "Significance of microRNAs and microRNA maturation regulators in breast cancer". Thesis, University of Nottingham, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.594865.
Texto completoArseni, Varvara. "MicroRNAs and the canonical microRNA biogenesis pathway in the planarian Schmidtea mediterranea". Thesis, University of Nottingham, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.581999.
Texto completoSætrom, Ola. "Predicting MicroRNA targets". Thesis, Norwegian University of Science and Technology, Department of Computer and Information Science, 2005. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-9266.
Texto completoMicroRNAs are a large family of short non-encoding RNAs that regulated protein production by binding to mRNAs. A single miRNA can regulate an mRNA by itself, or several miRNAs can cooperate in regulating the mRNAs. This is all dependent on the degree of complementarity between the miRNA and the target mRNA. Here, we present the program TargetBoost that, using a classifier generated by a combination of hardware accelerated genetic programming and boosting, allows for screening several large dataset against several miRNAs, and computes a likelihood of that genes in the dataset is regulated by the set of miRNAs used in the screening. We also present results from comparison of several different scoring functions for measuring cooperative effects. We found that the classifier used in TargetBoost is best for finding target sites that regulate mRNAs by themselves. A demo of TargetBoost can be found on http://www.interagon.com/demo.
BERTOLAZZI, Giorgio. "MicroRNA Interaction Networks". Doctoral thesis, Università degli Studi di Palermo, 2021. http://hdl.handle.net/10447/498927.
Texto completoBertolazzi’s thesis focuses on developing and applying computational methods to predict microRNA binding sites located on messenger RNA molecules. MicroRNAs (miRNAs) regulate gene expression by binding target messenger RNA molecules (mRNAs). Therefore, the prediction of miRNA binding is important to investigate cellular processes. Moreover, alterations in miRNA activity have been associated with many human diseases, such as cancer. The thesis explores miRNA binding behavior and highlights fundamental information for miRNA target prediction. In particular, a machine learning approach is used to upgrade an existing target prediction algorithm named ComiR; the original version of ComiR considers miRNA binding sites located on mRNA 3’UTR region. The novel algorithm significantly improves the ComiR prediction capacity by including miRNA binding sites located on mRNA coding regions.
Ammari, Meryem. "Rôle de miR-146a dans la régulation des fonctions monocytaires dans l’arthrite". Thesis, Montpellier 1, 2014. http://www.theses.fr/2014MON1T020.
Texto completoIntroduction : Monocytes represent a prototypic cell type when investigating the interplay between immune and skeletal systems as they can give rise to different cell types including dendritic cells, macrophages and osteoclasts (OC), which play key roles in immunity and bone homeostasis. Circulating monocytes consist of at least two main functional subsets, Ly6Chigh and Ly6Clow monocytes. It has been suggested that OC might develop preferentially from the Ly6Chigh monocyte subset, which excessive and prolonged activation is a hallmark of many inflammatory diseases. Among key molecular rheostats of cell fate, micro(mi)RNAs are a class of regulatory RNAs that control basic biological functions and orchestrate inflammatory responses. Few miRNAs have been involved in osteoclastogenesis. The present study aimed at investigating the role of miRNAs in osteoclastogenesis in the context of monocyte subsets, under steady state and inflammatory conditions. Methods & Results : Using genome-wide miRNA expression study we have identified miRNAs and putative targeted pathways that are differentially expressed between Ly6Chigh and LyC6low FACS sorted mouse monocytes, and common to their human counter parts CD14+CD16- and CD14dimCD16+ monocytes, respectively. Among these, miR-146a showed higher expression in Ly6Clow monocytes when compared to Ly6Chigh monocytes. Under inflammatory arthritis conditions, expression of miR-146a in Ly6Chigh monocytes was down regulated as compared to healthy controls. Using mouse deficient for miR-146a, we showed that knockdown of miR-146a increased OC differentiation in vitro. While no bone phenotype was evidenced in miR-146a deficient mice, nor under steady state or ovariectomized conditions, arthritis-induced bone resorption and bone loss were increased in miR-146a knockout mice. Finally, using a liposomal formulation able to delivermiR-146a mimics to Ly6Chigh monocytes upon intravenous injection, we showed that enforced expression of miR-146a led to decreased number of TRAP positive cells within the synovium of arthritic mice, and efficiently reduced bone erosion in inflammatory arthritis. This effect was associated with decreased RelB expression in miR-146a-overexpressing Ly6Chigh osteoclast progenitors. Conclusion : Overall, our results show that specific over-expression of miR-146a in Ly6Chigh monocytes altered OC differentiation and decreased bone erosion in inflammatory arthritis. These data suggest a novel role for miR-146a in controlling osteoclast fate of Ly6Chigh monocyte progenitors and that reduced miR-146a expression in Ly6Chigh monocytes under arthritic conditions contributes to pathogenic bone loss. Finally, delivery of miR-146a mimics to Ly6Chigh monocytes may offer valuable therapeutic potential to interfere with pathological bone loss
Dogini, Danyella Barbosa. "Quantificação de diferentes microRNAs no sistema nervoso central = implicações nos mecanismos de desenvolvimento e processos fisiopatologicos". [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/309739.
Texto completoTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: MicroRNAs são moléculas recém-descobertas de RNA não-codificadores que possuem de 21 a 24 nucleotídeos e que regulam a expressão após a transcrição dos genes alvo. Essa regulação pode ser realizada através da inibição da tradução ou da degradação do RNA mensageiro. Os miRNAs estão envolvidos em vários processo biológicos como, diferenciação celular e desenvolvimento embrionário, além de apresentarem expressão tecido e tempo-específica. Eles podem regular a expressão de pelo menos 1/3 de todos os genes humanos e estão envolvidos com a regulação do metabolismo e da apoptose. Os miRNAs são a chave como reguladores pós-transcricionais da neurogênese; estudos mostram que eles possuem a expressão associada com a transição entre proliferação e diferenciação e também tem expressão constitutiva em neurônios maduros, evidenciando o envolvimento dessas moléculas com o desenvolvimento do sistema nervoso central (SNC). Outros miRNAs estão sendo estudados e verifica-se que eles agem como reguladores de genes envolvidos em doenças como Alzheimer, Parkinson e, provavelmente, também devam possuir um papel na regulação das epilepsias. No primeiro trabalho, apresentado no segundo capítulo, investigamos o papel dos miRNAs no desenvolvimento do SNC através da quantificação de 104 miRNAs em cérebros em desenvolvimento de camundongos. No segundo trabalho, apresentado no terceiro capítulo, para analisarmos o papel dos miRNAs na epilepsia de lobo temporal, verificamos se havia presença de miRNAs com expressão diferenciada entre tecidos removidos de pacientes que se submeteram a cirurgia de hipocampectomia e tecidos normais provenientes de autópsias. Para ambos os experimentos, foram extraídos os RNAs dos tecidos e quantificados por PCR em tempo real com o kit MicroRNA Assay baseado em iniciadores com estrutura em stem loop. Nos camundongos, análises de bioinformática encontraram quatro cluster de acordo com a expressão dos miRNAs. Um cluster (C1) com 12 miRNAs (miR-9; miR-17- 5p; miR-124a; miR-125a; miR-125b;miR-130a; miR-140; miR-181a; miR-199a; miR-205; miR-214; miR-301) apresentou expressão com diferença significativa durante o desenvolvimento. Nos tecidos dos pacientes, após a análise de bioinformática, encontramos três miRNAs com expressão diferenciada entre pacientes e controle (miR-29b, miR-30d e let-7). Em ambos os experimentos analisamos os possíveis genes alvo desse miRNAs. Nos camundongos, nossos resultados sugerem a presença de um padrão específico de expressão no cluster C1, indicando que esses miRNAs possam ter um papel na regulação de genes envolvidos na neurogênese. Nos tecidos humanos, os genes alvo encontrados estão envolvidos, principalmente, em proliferação celular, neurogênese e apoptose, indicando uma provável atuação dos miRNAs na regulação de genes que estão envolvidos na epilepsia de lobo temporal
Abstract: MicroRNAs are a new class of small RNA molecules (21-24 nucleotide-long) that negatively regulate gene expression either by translational repression or target mRNA degradation. It is believed that about 30% of all human genes are targeted by these molecules. MiRNAs are involved in many important biological processes including cell differentiation, embryonic development and central nervous system formation, besides they showed specific temporal-space expression. They can regulate 1/3 of human genes and are involved in metabolism and apoptosis. miRNAs are the key as neurogenesis postranscriptional regulation; studies previous indicates miRNA expression associate with proliferation and differentiation in development of central nervous system (CNS) and housekeeping expression in mature neurons. They are involved in several diseases as Alzkeimer's and Parkinson and may have a role in epilepsy regulation. In second chapter, we analyze the miRNA expression in mouse brain during four stages of CNS development; in third chapter, we analyze hippocampal tissue of four patients who underwent selective resection of the mesial temporal structures for the treatment of clinically refractory seizures. In addition we used control samples from autopsy (n=4) for comparison. In both experiments, total RNA was isolated from tissues and used in real-time PCR reactions with TaqMan¿ microRNA assays (Applied Biosystems) to quantify 104 (mouse brain) or 157 (human tissue) different miRNAs. In mouse brain analysis, we were able to identified four different clusters (C1, C2, C3 and C4) of miRNAs expression. Significant differences in expression during development were observed only in miRNAs included in C1. Our results suggest the presence of a specific expression pattern in C1, indicating that these miRNAs could have an important role in gene regulation during neurogenesis. We found a significant decrease (p<0,05) in expression of 12 miRNAs (miR-9; miR-17-5p; miR-124a; miR-125a; miR-125b;miR-130a; miR-140; miR-181a; miR-199a; miR-205; miR-214; miR- 301) belonging to cluster C1 in latter stages of development. Computational target identification showed that 10 of the 12 miRNAs present in C1 could be involved in neurogenesis. In human tissues, bioinformatics analyzes identified three miRNAs species which were differently expressed in patients as compared to controls: let7a was over expressed in patients (4 fold increased), miR-29b and miR-30d were down-regulated in patients (2.5 fold and 0.5 fold decreased, respectively). Possible target genes for let-7a are NME6 and NCAM1 (which would be down-regulated in patients); for miR-29b is MCL-1 and for miR30d are CTNND2, LGI1 and SON (which would be up-regulated in patients). We have identified three different miRNA species differently expressed in hippocampal sclerosis. Gene functions related to the possible miRNA targets are involved mainly with cell proliferation, neurogenesis, cell adhesion and apoptosis. Our results indicate new molecular targets which should be explored in additional studies addressing miRNA regulation in hippocampal sclerosis
Doutorado
Neurociencias
Doutor em Fisiopatologia Medica
Wang, Qi. "Using Imputed Microrna Regulation Based on Weighted Ranked Expression and Putative Microrna Targets and Analysis of Variance to Select Micrornas for Predicting Prostate Cancer Recurrence". Thesis, North Dakota State University, 2014. https://hdl.handle.net/10365/27341.
Texto completoKwan, Chun-kit Peter y 關駿傑. "The expression of microRNA-34c and microRNA processing enzymes in preimplantation embryos". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B44659283.
Texto completoD'Ario, G. "IDENTIFICATION OF INTRONIC MICRORNAS ALTERED IN BREAST CANCER THROUGH MICROARRAY HOST GENE EXPRESSION ANALYSIS". Doctoral thesis, Università degli Studi di Milano, 2011. http://hdl.handle.net/2434/157939.
Texto completoSmith, Daniel. "Electrochemical detection of microRNA". Thesis, Cardiff University, 2017. http://orca.cf.ac.uk/107718/.
Texto completoMigault, Mélodie. "La séquestration de microARN dans le mélanome métastatique : du mécanisme moléculaire au candidat thérapeutique". Thesis, Rennes 1, 2017. http://www.theses.fr/2017REN1B014/document.
Texto completoMicroRNAs (miRNAs) are small non-coding RNAs. They fine tune gene-expression through specific complementary interaction with their RNA targets. The miRNA repressive function towards a given RNA is highly regulated and in part dependent on the abundance of its other targets competing for miRNA’s binding. Some of these competing endogenous RNAs (ceRNAs) can resist to miRNA-mediated RNA decay thereby sequestering miRNAs. They are named miRNA sponges. Deregulation of ceRNAs and miRNA sponges networks are implicated in many pathologic processes including cancer. My PhD work focused on miRNA sequestration in cutaneous melanoma. Melanomas arise from the malignant transformation of melanocytes; the skin-cell specialized in pigment production. Most melanoma undergoes metastatic evolution, with metastatic cells spreading rapidly in the entire organism (lymph node, liver, lungs, brain, etc.). Early and complete resection of primary in situ melanoma is thus determinant for patient outcome. Since 2010, potent therapeutic options have been developed. Unfortunately, patients ultimately develop resistance while some are non-responders. There is thus an urgent need to develop new therapeutic strategies to treat metastatic melanoma. We have identified that the Tyrosinase Related Protein 1 (TYRP1) mRNA function as a miRNA sponge. TYRP1 is specifically expressed in the melanocytic lineage. TYRP1 mRNA governs melanoma growth endorsing thereby a non-coding function. We demonstrated that TYRP1 mRNA sequesters the tumor suppressor miR-16 via non-canonical miRNA binding sites (MREs-16). Non-canonical miR-16 binding lacks mRNA decay function favoring TYRP1 mRNA stability and miRNA sequestration. Sequestered miR-16 can no more repress its canonical targets involved in cell proliferation and tumor growth. To reset miR-16’s activity and block melanoma growth, we used “Target Site Blocker” (TSB). TSBs are modified antisense oligonucleotides with enhanced stability and affinity to its target. We designed a TSB, named TSB-T3, overlapping specially TYRP1 non-canonical MRE-16. We first showed that TSB-T3 binds to TYRP1 mRNA and competes with miR-16. Freed miR-16 binds to its canonical targets inducing their decay. TSB-T3 blocks melanoma cell growth in vitro and in vivo, using patient-derived tumor xenograft. We thus showed for the first time that TSB’s strategy redirecting a tumor suppressor miRNA is a potent tool to monitor metastatic melanoma growth. Together my PhD work brings out a new oncogenic mechanism based on miRNA sequestration and proposes an original strategy of targeted therapy against metastatic melanoma
Aggarwal, Neha. "Characterization of a microRNA Harboring Intron for pre-mRNA Splicing and microRNA Processing". Cleveland State University / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=csu1275407397.
Texto completoPellegrino, Loredana. "Distinct functional roles of microRNA-23b and microRNA-26a in breast cancer pathogenesis". Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/24827.
Texto completoFrackowiak, Agnieszka. "Involvement of microRNA-30 family in metastatic dissemination of breast cancer cells to bone". Thesis, Lyon 1, 2015. http://www.theses.fr/2015LYO10106/document.
Texto completoBone metastasis is a common complication of advanced breast cancers and is clinically responsible of bone fractures, hypercalcemia and pain for which only palliative therapies are proposed. Breast tumor cells that preferentially invade bone express a set of deregulated genes that enhance bone tropism and facilitate bone marrow engraftment which may lead to the formation of overt osteolytic lesions. Molecular pathways underlining these steps are regulated through the tight control of genes expressed by cancer cells interacting with cells from the bone microenvironment. In this context, microRNAs act as regulators of gene expression and control multiple aspects of bone metastasis, including tumor cell escape from the primary site, dissemination, invasion of the bone marrow and secondary outgrowth. MicroRNA transcriptomic profiling of osteotropic breast cancer cell lines identified drastic down-regulation of the miR-30 family (miRs-30). In the clinic, low expression of miRs-30 in breast primary tumors is associated with poor distant metastasis-free survival and hormoneinsensitive status. In a model of human bone metastasis in vivo, the forced expression of miRs-30 in a breast cancer cell line that is highly and specifically metastatic to bone inhibited bone metastasis. We demonstrated that miRs-30 inhibit tumor cell invasiveness and stimulate osteoblastogenesis, in vitro, and reduces tumor burden and osteoclast activity, in vivo. Consistent with that, the expression of several genes that promote bone metastasis were inhibited by miRs- 30. Among these, expression of connective tissue growth factor (CTGF) was up-regulated in human bone metastasis. The early steps of bone metastasis were studied in a mouse model using spontaneously metastatic mouse breast cancer cell lines inoculated in the mammary gland. In this model, miRs-30 did not alter tumor growth or metastatic dissemination to bone. However, miRs-30 inhibited cell invasiveness and cancer stem cell-like phenotype of these metastatic cells. We conclude that miRs-30, by interfering negatively with bone metastasis, represent a potential therapy to repress gene targets that promote bone metastasis
Robinson, Hollie Christine. "Investigation of the role of microRNA-143 and microRNA-145 in acute vascular injury". Thesis, University of Glasgow, 2014. http://theses.gla.ac.uk/5221/.
Texto completoKemp, Jacqueline Renee. "Genome-wide Angiotensin II regulated microRNA expression profiling: A smooth muscle-specific microRNA signature". Cleveland State University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=csu1367845628.
Texto completoAzevedo-Pouly, Ana Clara P. "Biological functions of microRNA-216 and microRNA-217 during the development of pancreatic cancer". The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1374244806.
Texto completoSiciliano, Velia. "A microRNA based genetic clock". Thesis, Open University, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.552785.
Texto completoWeinstein, Earl G. 1974. "MicroRNA cloning and bioinformatic analysis". Thesis, Massachusetts Institute of Technology, 2002. http://hdl.handle.net/1721.1/8390.
Texto completoIncludes bibliographical references.
Part I. Two gene-regulatory noncoding RNAs (ncRNAs), let-7 RNA and lin-4 RNA, were previously discovered in the C. elegans genome. The let-7 gene is conserved across a wide range of genomes, suggesting that these ncRNAs represent a wider class of gene-regulatory RNAs. Both lin-4 and let-7 RNAs are generated from stem-loop precursor RNAs, and share a common biochemical signature, namely 5'-terminal phosphate and 3'-terminal hydroxyl groups. We refer to ncRNAs that share the characteristic size, biochemical signature, and precursor structures of let-7 and lin-4 as microRNAs (miRNAs). The size of this class of genes, and its prevalence in other genomes, are unknown. Therefore, we developed an experimental and bioinformatics strategy to identify novel miRNA genes. We discovered a total of 75 miRNA genes in the C. elegans genome, and orthologues for a majority of these were computationally identified in the C. briggsae, D. melanogaster or H. sapiens genomes. Northern analysis was used to confirm and analyze the expression of these miRNAs. The data set has implications for understanding miRNA gene regulation, miRNA processing, and regulation of miRNA genes. Part II. Directed molecular evolution has previously been applied to generate RNAs with novel structures and functions. This method works because nucleic acids can be selected, randomized, amplified and characterized using polymerase chain reaction (PCR)-based methods. Here we present a novel method for extending directed molecular evolution to the realm of peptide selections by linking a peptide to its encoding mRNA.
(cont.) A proof of principle selection for two different peptides indicates that this tRNA should prove useful in discovering more complex protein molecules using directed molecular evolution.
by Earl G. Weinstein.
Ph.D.
Torres, Adrian Gabriel. "MicroRNA targeting with oligonucleotide analogues". Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610040.
Texto completoMorton, Sarah Uhler. "MicroRNA regulation of cardiac development". Diss., Search in ProQuest Dissertations & Theses. UC Only, 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3311351.
Texto completoChen, Jianfu Wang Da-zhi. "MicroRNA function in muscle development". Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2008. http://dc.lib.unc.edu/u?/etd,2013.
Texto completoTitle from electronic title page (viewed Feb. 17, 2009). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Cell & Developmental Biology of School of Medicine." Discipline: Cell and Developmental Biology; Department/School: Medicine.
Hunter, Catriona Mhairi. "MicroRNA regulation of macrophage activation". Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/31027.
Texto completoPERBELLINI, RICCARDO. "I MICRORNA NELLE DISTROFIE MIOTONICHE". Doctoral thesis, Università degli Studi di Milano, 2010. http://hdl.handle.net/2434/150059.
Texto completoFrölich, Anne. "Der Einfluss körperlichen Trainings auf die endotheliale Dysfunktion mit Fokus auf die Rolle der microRNA-21 und microRNA-126 im herzinsuffizienten Mausmodell". Doctoral thesis, Universitätsbibliothek Leipzig, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-166793.
Texto completoMassiere, Jessica. "La transition épithélio-mésenchymateuse dans les cellules épithéliales gastriques : rôle des microARN régulés par Helicobacter pylori". Thesis, Bordeaux 2, 2011. http://www.theses.fr/2011BOR21835/document.
Texto completoMicroRNA are small noncoding RNA that post-transcriptionally regulate gene expression. Due to their high regulator potential, a change in their expression may lead to the emergence of diseases such as cancer or inhibition of defense mechanisms against pathogens. Our aim is to characterize the role of miRNA in the response of gastric eptithelial cells to Helicobacter pylori (H. pylori). Indeed, H. pylori promote gastric adenocarcinoma and MALT lymphoma. Its virulence is essentially mediated by CagA, injected into cells of the gastric mucosa. Thanks to high throughput sequencing of miRNA content of a gastric epithelial cell line, infected or not with H. pylori: miR-200b and -200c appeared up-regulated upon infection. These miRNA are potent inhibitors of the “epithelial-to-mesenchymal transition” (EMT), a process that drastically alters cell morphology and promotes cell invasion. MiR-200b/c target the transcription factors ZEB1 and ZEB2, with which they are involved in a mutually repressive feedback loop. In basal conditions, the high levels miR-200b/c in gastric epithelial cells totally silence ZEB1 mRNA whereas H. pylori promotes EMT via ZEB1 expression, on the dependence of CagA translocation into host cells. But, paradoxically, miR-200b/c levels were also up-regulated upon infection. The increased miR-200b/c levels in infected cells moderate ZEB1 induction thanks to NF-kB activation and constitute a self-defense mechanism to thwart the loss of their epithelial phenotype upon infection
Guérit, David. "Rôle des miR-29a et miR-574-3p au cours de la différenciation chondrocytaire de la cellule souche mésenchymateuse". Thesis, Montpellier 1, 2012. http://www.theses.fr/2012MON1T013/document.
Texto completoRoles of miR-29a and miR-574-3p during the chondrogenic differentiation of mesenchymal stem cells. With the constant increase of the lifespan, osteoarticular pathologies such as osteoarthritis or rheumatoid arthritis, characterized by articular cartilage degradation, are important public health problems. In absence of spontaneous regeneration, cartilage engineering approaches are being considered. Current techniques rely on autologous chondrocyte transplantation but in the majority of cases, this approach gives similar results as current surgeries. Due to their capacity of differentiation toward chondrocytes, mesenchymal stem cells (MSC) represent a new source of cells with therapeutic potential. However, production of a functional cartilage in vivo after implantation of expanded MSC is hampered by the difficulty to reproduce the complexity of the differentiation process to get mature chondrocytes from MSC. The objective of my Ph.D thesis aimed to identify micro-RNAs (miRNAs) modulated during chondrogenic differentiation of primary human MSCs and to study their role as well as their regulation in this process. We identified two miRNAs: miR-29a whose expression decreases progressively during the differentiation and miR-574-3p whose expression rapidly increases and stays constant until the end of the differentiation. Both miRNAs are regulated by the transcription factor Sox9 but in an opposite manner: Sox9 inhibits miR-29a and induces miR-574-3p. We show that YY1 directly interact with Sox9 to regulate miR-29a but not miR-574-3p; this interaction likely explaining the opposite effects of Sox9 on miR-29a and miR-574-3p expression. Moreover we showed that miR-29a and miR-574-3p are both inhibitors of chondrogenesis and we identified FOXO3A and RXRα as their respective targets. In conclusion, we identified two new miRNAs which are regulated by Sox9 and inhibitors of chondrogenesis. They act through the modulation of two target genes, whose role during chondrogenic differentiation of adult MSC was previously not characterized
Kamrath, Malte [Verfasser]. "Dynamischer biomechanischer Stretch führt zur Regulation von microRNA-146a und microRNA-503 in Kardiomyozyten / Malte Kamrath". Kiel : Universitätsbibliothek Kiel, 2019. http://d-nb.info/1187732788/34.
Texto completoSzczyrba, Jaroslaw [Verfasser] y Friedrich [Akademischer Betreuer] Grässer. "Das MicroRNA-Profil des Prostata-Karzinoms und Identifizierung von microRNA-Zielgenen / Jaroslaw Szczyrba. Betreuer: Friedrich Grässer". Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2012. http://d-nb.info/1052557279/34.
Texto completoShcheholeva, Iryna. "Synthèse orientée vers la diversité pour l'inhibition de microARN oncogènes". Electronic Thesis or Diss., Université Côte d'Azur, 2024. https://intranet-theses.unice.fr/2024COAZ5006.
Texto completoConstituting a major part of the transcriptional output and given their function in modulation of epigenetics, noncoding RNAs (ncRNAs) carry an important role in disease development, but remain under-exploited biological targets. MicroRNAs (miRs) are 19 - 25 nucleotide long single-stranded RNAs and represent a major ncRNA family that is primarily known for their role in the control of gene expression. Each microRNA indeed inhibits translation of multiple messenger RNAs, and dysregulation of microRNAs is critical to pathogenesis and oncogenesis in particular. Specifically, microRNA-21 has been in the spotlight after its consistent overexpression in cancers as reported in a study that profiled 540 clinical samples from cancer patients. Thus, inhibition of miR-21 function holds the promise for both an efficient therapy alone and as an adjuvant to the existing treatments.The goal of this PhD work was to develop a small-molecule inhibitor of this oncogenic microRNA, tackling the last step of its biogenesis, an enzymatic cleavage by Dicer. We focused on the latter to mitigate a challenge associated with ssRNA as a biological target, such as the undefined secondary structure. In this thesis, the precursor of miR-21, a longer and structured preceding transcript, was used as a target and small-molecule ligands were designed to bind to its structured regions and impede its recognition via Dicer. The library of the drug-like RNA-focused ligands was designed de novo and synthesised using efficient catalytic methodologies and their activity was assessed in vitro using fluorescence-based biochemical assays with human recombinant Dicer. The study revealed several novel small molecule binders and inhibitors of oncogenic microRNA-21 in the low micromolar range. The binding mechanism of the best compounds was studied with biophysical and in silico methods to establish structure-activity relationships and improve the observed activity. This thesis discloses new promising scaffolds that inhibit miR-21 maturation of miR-21 in vitro and provide a blueprint for targeting this noncoding RNA with small molecules
Boggs, Rene' Michelle. "MicroRNA expression in canine mammary cancer". Diss., Texas A&M University, 2008. http://hdl.handle.net/1969.1/85979.
Texto completoO'Connor, Anna Maria. "MicroRNA regulation of endothelial calcium signalling". Thesis, Queen's University Belfast, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.602716.
Texto completoTudor, Hannah Rachael. "Characterisation of a spliced tomato microRNA". Thesis, University of East Anglia, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.578250.
Texto completoChow, Wang-ngai y 周弘毅. "Identification of microRNA in penicillium marneffei". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/198803.
Texto completopublished_or_final_version
Microbiology
Doctoral
Doctor of Philosophy
Dawkins, Sam. "MicroRNA release in acute myocardial infarction". Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:a0a82298-45e5-4f66-b368-446cad9726ae.
Texto completoThomas, Jordan M. "The role of microRNA in cancer". Thesis, Boston University, 2013. https://hdl.handle.net/2144/21261.
Texto completoMicro ribonucleic acids (miRNAs) are pivotal post-transcriptional regulators of gene expression and if research continues to reveal positive results, they will soon be used as therapeutic targets in the clinical setting for the treatment of a variety of cancers. They are evolutionarily conserved small noncoding RNAs that range from 18 to 24 nucleotides in length. There are over 1,400 miRNAs for which abundant evidence has demonstrated fundamental importance in normal cell development and up- or downregulation when they become deregulated. The deregulation of miRNAs, which can function as tumor suppressors or oncogenes, contributes to the development of cancer, among other diseases. Deregulation of tumor suppressor miRNA can occur in many different tissues of the body and lead to a variety of cancers. Tumor suppressor let-7 negatively regulates expression of an oncogenic mRNA named RAS. In lung cancer, a decrease in let-7 produces an increase in expression of RAS, which contributes to cell proliferation and tumorigenesis. In chronic lymphocytic leukemia, Bcl2 protein becomes overexpressed due to the down-regulation of tumor suppressors miRNA-15 and miRNA-16. MicroRNA-34 plays an important role in neuroblastoma in which its expression is decreased due to mutations that decrease a tumor suppressor protein, p53. Upon deregulation of oncogenic miRNAs, tumor suppressor mRNA expression is decreased and leads to multiple types of cancer. Up-regulation of the miRNA-17-92 cluster in lung cancer leads to increased cell proliferation and contributes to angiogenesis in many cancers. In B cell lymphoma, miRNA-155 becomes up-regulated along with an RNA named BIC. This up-regulation accelerates pathogenesis and up-regulation of an oncogenic protein, c-myc. MicroRNA-21 acts as an anti-apoptotic factor by downregulating apoptosis-related genes and contributing to the development of human glioblastoma. This review summarizes the present understanding of how miRNAs function at the molecular level in the body, how their deregulation contributes to tumor formation, maintenance and metastasis and how they can be used for cancer diagnosis, prognosis and therapy. With the mass amounts of knowledge gained from the current research done on miRNAs, a cancer cure may soon be developed based on the targeting of specific miRNAs. The promise of miRNAs in cancer therapeutics will depend on the development of proper delivery strategies of miRNA mimics and inhibitors, in addition to evaluation of safe usage and toxicity of therapeutic dosages.
2031-01-01
Jurcevic, Sanja. "MicroRNA expression profiling in endometrial adenocarcinoma". Doctoral thesis, Örebro universitet, Institutionen för hälsovetenskap och medicin, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-41640.
Texto completoHilton, Catriona. "MicroRNA-196a in human adipose tissue". Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:a1a7a7a6-09a2-422f-b900-e133004193da.
Texto completoKaimal, Vivek. "Computational approaches to study microRNA networks". University of Cincinnati / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1298041682.
Texto completoPomyen, Yotsawat. "Exploring microRNA biology using integrative bioinformatics". Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/24774.
Texto completoAdai, Alex Tamas. "Uncovering microRNA function through data integration". Diss., Search in ProQuest Dissertations & Theses. UC Only, 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3311333.
Texto completoGASPARELLO, Jessica. "Novel trands in microRNA based theranostics". Doctoral thesis, Università degli studi di Ferrara, 2018. http://hdl.handle.net/11392/2478767.
Texto completoMiRNAs are a class of small non-coding RNA of about 19-23 nucleotides in length able to act as regulators of gene expression thanks to their ability to bind the 3’UTR which results in inhibition of translation or in mRNA degradation. Due to their short sequence, they can bind more than one transcript, so they may be involved in more than one biological pathway. Since their first identification in 1993, they have been associated to a long list of physiological or pathological conditions. The dysregulation of miRNA profile may be associated to several diseases, so therapies based on the restore of physiological miRNA levels may have huge impact on several pathologies, for this reason molecules able to both increase or decrease miRNA levels have been recently developed. Through miRNAs levels regulation is possible to indirectly regulate their targets levels. This evidence was investigated in this thesis to reduce levels of BCL11A, one of the principal repressor of γ-globin gene. The following key results: a) miR-210 interaction with BCL11A coding region was demonstrated with SPR-based analysis, b) the increase of miR-210 intracellular levels leads to a decrease of BCL11A transcript and protein, encouraged us to consider the employment of miR-210 mimicking molecules as possible therapeutic approach to reduce BCL11A expression in the field of β-thalassemia treatment. Modulation of miRNAs levels into cells can be achieve with different kinds of molecules and most of them generally require an appropriate vehicle. At this propose we investigated with encouraging results a calixarene-based structure compound called ML122, previously used for DNA delivery, to vehicle miRNA-based molecules and PNAs. a) High transfection efficiency, associated with b) evident biological effects obtained when both premiRNA molecules and PNAs are vehicled with ML122, allow us to consider ML122 as a possible alternative to commercial available transfection agents. MiRNAs are present not only into cells but as demonstrated by Chim and colleagues they were found also in several body fluids, including plasma, in which have been demonstrated to be very stable. Several groups employed circulating miRNAs at diagnostic or prognostic propose opening a new important issue in the field of the non-invasive diagnostic techniques. In the present thesis we employed the non-invasive diagnostic technique in two different fields. First, we considered circulating miRNA in colorectal cancer diagnosis and management. In this section, three important massages were obtained a) miRNA are normally released by cells, the release pattern is different in each cell line and often differs from the miRNA pattern into cells, b) a comparison between two different techniques, RTqPCR and ddPCR, demonstrates how the two techniques gave comparable results, even if ddPCR for technical issue is more suitable for miRNA quantification in plasma samples, c) analysis of the three selected miRNAs in CRC patients and healthy controls demonstrates how additional miRNAs (at 6 or 7 miRNAs) are needed to identify patterns associated to CRC patients. The analysis of cmiRNAs was also, not applied to a health problem but to identify an illicit practice in sport such as autologous blood transfusion. The analysis of a limited number of samples using a high-throughput miRNA analysis method, i.e. microarray, allow us to identify two different list of miRNAs possible biomarkers for the detection of ABT: (a) a list of 8 miRNAs which modulation may be related to different oxygen availability immediately after the two key steps of ABT practice i.e. blood withdrawal and blood reinfusion. Moreover, a second list (b) was obtained considering all expressed miRNAs in our plasma samples. Despite the number of analysed samples is limited (6 ABT trained subjects and 3 control pools) preliminary encouraging data were obtained, which of course need to be confirmed increasing the samples size.
SOKOLOVA, VIKTORIJA. "MICRORNA INVOLVEMENT IN COLON CANCER PROGRESSION". Doctoral thesis, Università degli Studi di Milano, 2012. http://hdl.handle.net/2434/214611.
Texto completoStuchi, Nathália Maciel Maniezzo [UNESP]. "Avaliação da Anexina A1, FPR1, FPR2 e miRNAs em adenocarcinoma gástrico". Universidade Estadual Paulista (UNESP), 2016. http://hdl.handle.net/11449/141940.
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Apesar do declínio da incidência, o câncer gástrico ocupa ainda a terceira posição em causa de morte por câncer no mundo, tendo como principal fator de risco a bactéria Helicobacter pylori. Esta bactéria pode levar a uma inflamação persistente através da produção de citocinas pró-inflamatórias e de espécies reativas de oxigênio e nitrogênio, estimulando a proliferação celular bem como outros processos envolvidos na carcinogênese. Ainda envolvidos nestes processos tem sido observada a participação de microRNAs, que exercem papel importante na regulação pós-transcricional, influenciando processos fisiológicos normais da célula bem como aqueles ligados às doenças, como por exemplo o câncer gástrico. Alguns miRNAs podem atuar como oncogenes, genes supressores de tumor e biomarcadores para diversas patologias, podendo alvejar genes relacionados com inflamação e câncer como o gene ANXA1 (Anexina-A1). A Anexina-A1 é uma proteína anti-inflamatória e com ação anti-proliferativa, que se liga à receptores do tipo formil peptídeo como por exemplo FPR1 e FPR2, ambos sabidamente relacionados com a progressão de doenças como o câncer. Desta forma o presente trabalho teve como objetivos avaliar a expressão da proteína Anexina A1 e seus receptores FPR1 e FPR2, bem como avaliar a expressão do RNAm da ANXA1 e de miRNAs que possam modular a expressão desse gene (hsa-mir-27a, hsa-mir-196a e hsa-mir-222) em adenocarcinoma gástrico e correlacionar estes resultados com os aspectos clínico-patológicos. Foram avaliadas 31 amostras de adenocarcinoma gástrico, assim como as regiões metaplásica ou normal adjacentes ao tumor. A quantificação relativa (RQ) do RNAm da ANXA1 e miRNAs foi realizada por PCR quantitativo em tempo real utilizando ensaio TaqMan, e a expressão proteica da AnxA1, FPR1 e FPR2 por imuno-histoquímica e análise densitométrica. Em relação à expressão gênica relativa foram observados o aumento da expressão da ANXA1 nos tumores (RQ=1,374; p<0,001), assim como do miR-196a que apresentou aumento de expressão tanto no tecido metaplásico (RQ= 4,784; p=0,0016) e tumoral (RQ=16,99; p< 0,001) em relação ao tecido normal. O miR-27a não se apresentou diferencialmente expresso nos diferentes tecidos e houve diminuição da expressão do miR-222 (RQ=0,687; p=0,01) no tecido tumoral em relação ao tecido normal. Apenas o miR-196a e a ANXA1 apresentaram correlação significantemente inversa (r= -0,55; p=0,003), e este miRNA foi o único que apresentou associação com o sexo feminino, devido aumento de expressão em mulheres. Quando se comparou a expressão relativa aos parâmetros clínico-patológicos e tumorais não foram encontradas diferenças significativas. Quanto à expressão proteica o FPR2 não apresentou marcação no tecido normal, metaplásico e tumoral. Contudo a AnxA1 e FPR1 apresentaram imunomarcação positiva amplamente distribuída no tecido tumoral e positivamente correlacionados tanto no epitélio (r=0,87; p<0,0001) como estroma (r=0,62; p=0,004). Portanto, nossos resultados sugerem que a ANXA1 é modulada pelo miR-196a em câncer gástrico, e evidenciam que tanto a AnxA1 como o FPR1 também estão envolvidos no processo de carcinogênese gástrica. Tais achados podem abrir possibilidades para futuros estudos sobre novos alvos terapêuticos já que AnxA1 e FPR1 são possíveis alvos farmacológicos, e as terapias baseadas em microRNAs tem sido amplamente pesquisadas.
Gastric cancer still ranks third in cause of cancer death worldwide, despite the decline in its incidence, being Helicobacter pylori the main risk factor for this disease. This bacterium can lead to persistent inflammation via the production of proinflammatory cytokines and reactive oxygen and nitrogen species, stimulating cell proliferation and other processes involved in carcinogenesis. Still involved in this process, it has been observed the participation of miRNAs, which play an important role in post- transcriptional regulation, influencing normal physiological processes of the cell as well as those linked to diseases such as gastric cancer. Some miRNAs can act as oncogenes, tumor suppressor genes and biomarkers for various diseases, can targetting genes linked to inflammation and cancer such as ANXA1 gene (Annexin A1). Annexin A1 is an anti-inflammatory protein with anti-proliferative action that binds to formyl peptide receptors such as, FPR1 and FPR2, both known to be related to the progression of diseases such as cancer. Thus, the present study aimed to evaluate the expression of Annexin A1, FPR1 and FPR2 receptors, and the expression of mRNA ANXA1 and miRNAs (hsa-mir-27a, hsa-mir-196a and hsa-miR 222) in gastric adenocarcinoma, also correlate these results to the clinicopathological features. 31 adenocarcinoma samples were evaluated, as well as normal or metaplastic region adjacent to the tumor. Relative quantification (RQ) of miRNA and mRNA ANXA1 was evaluated by TaqMan assay and protein expression AnxA1, FPR1 and FPR2 by immunohistochemistry and densitometry analysis. Regarding the relative expression the following results were observed, increased expression in tumors of ANXA1 (RQ = 1.374; p < 0.001) and miR- 196a that showed increased expression it he metaplastic tissue (RQ = 4.784; p = 0.0016) and tumor (RQ = 16.99; p < 0.001) compared to normal tissue. The miR- 27a did not appear differentially expressed in different tissues and there was a decrease of miR -222 expression (RQ = 0.687; p = 0.01) in tumor tissue compared to normal tissue. Only the miR-196a and ANXA1 presented a significant inverse correlation (r = -0.55; p = 0.003), and this miRNA was the only one that showed association to female gender, due to increased expression in women when comparing the relative expression to clinicopathological parameters and tumor features. The FPR2 was not expressed in normal, metaplasic and tumor tissue. However, the AnxA1 and FPR1 were widely distributed positive immunostaining in tumor tissue and positively correlated both in the epithelium (r = 0.87 ; p < 0.0001) and stromal (r = 0.62 ; p = 0.004). Thus, our results suggest that ANXA1 is modulated by miR-196a in gastric cancer, and evidencing that both AnxA1 and FPR1 are also involved in gastric carcinogenesis process. These data open the possibility for future studies on new therapeutic targets since AnxA1 and FPR1 are adjustable pharmacological targets, and microRNAs ` therapies have been widely researched.
FAPESP: 2012/15036-8
CNPq: 474776/2013-1
Bertoni, Natália. "Perfil de expressão de microRNAs circulantes em carcinomas de fígado, pâncreas e vias biliares". Botucatu, 2017. http://hdl.handle.net/11449/148864.
Texto completoResumo: Introdução: Os carcinomas hepato-pancreato-biliares (HPB) são carcinomas agressivos, com células progenitoras comuns, sugerindo que mecanismos moleculares de tumorigênese podem ser compartilhados entre estes tumores. Os microRNAs (miRNAs) são importantes reguladores da expressão gênica e têm sido investigados como potenciais biomarcadores diagnósticos, prognósticos e de resposta a tratamento de pacientes com câncer. O objetivo deste estudo foi identificar o perfil de expressão de miRNAs no plasma de pacientes com carcinomas HPB e potenciais processos biológicos envolvidos na tumorigênese destes carcinomas.Pacientes e Métodos: Foram analisadas 12 amostras de plasma, sendo 4 obtidas de pacientes com carcinoma hepatocelular, 4 com adenocarcinoma de pâncreas e 4 com colangiocarcinoma e 10 amostras de plasma de indivíduos saudáveis (grupo de referência). A expressão de miRNAs plasmáticos foi determinada por meio do ensaio TaqMan® Array Human MicroRNA Cards (card A, v3.0). Análises de predição de mRNAs-alvo potencialmente regulados pelos miRNAs identificados e redes de interação miRNAs-mRNAs-alvo foram geradas.Resultados: Dos 42 miRNAs com expressão desregulada no plasma de pacientes com carcinomas HPB comparados ao grupo de indivíduos saudáveis, 28 miRNAs (67%) são compartilhados entre os três subtipos tumorais, sendo: 19 com expressão diminuída e 9 com expressão aumentada. Os mRNAs-alvo preditos dos miRNAs com expressão alterada nos carcinomas HPB estão associados com importa... (Resumo completo, clicar acesso eletrônico abaixo)
Mestre
Davis, M. P. "Generation of a murine ES cell system deficient in microRNA processing for the identification of microRNA targets". Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.598389.
Texto completoHart, Martin [Verfasser] y Friedrich [Akademischer Betreuer] Grässer. "Das komparative MicroRNA-Profil zunehmend maligner Prostatakarzinome und Identifizierung von microRNA-Zielgenen / Martin Hart. Betreuer: Friedrich Grässer". Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2014. http://d-nb.info/105372585X/34.
Texto completoKuwabara, Yasuhide. "Increased MicroRNA-1 and MicroRNA-133a Levels in Serum of Patients With Cardiovascular Disease Indicate Myocardial Damage". Kyoto University, 2012. http://hdl.handle.net/2433/157428.
Texto completoShenoy, Shamika. "Exosomal microRNA as a sepsis biomarker : Assessing different volumes of plasma for possible quantification of exosomal microRNA". Thesis, Högskolan i Skövde, Institutionen för biovetenskap, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-17523.
Texto completoPers, Yves-Marie. "Effet thérapeutique des cellules souches mésenchymateuses dans l'arthrose : mécanismes et translation clinique". Thesis, Montpellier, 2018. http://www.theses.fr/2018MONTT045.
Texto completoMesenchymal Stem Cells (MSCs) are stromal cells present in a number of different tissue types. In addition to their ability to differentiate into multiple lineages (chondrocytes, adipocytes and osteoblasts), MSCs also display immunosuppressive properties. Whilst these mechanisms are far from fully understood, their immunosuppressive capacity has recently been shown to be modulated by miRNAs. OA is the most common form of joint diseases without curative treatment and mainly characterized by the degradation of articular cartilage, with subchondral bone alterations and synovial inflammation. MSC might provide therapeutic potential for treatment of OA.Here, we showed that an autologous injection of adipose-derived MSC (ASC) into an osteoarthritic joint improved pain and function levels in patients. We underscored the systemic immune tolerance induced following intra-articular injections of ASCs. Finally, we investigated the miRNA expression profile of human MSCs upon their stimulation by peripheral blood mononuclear cells. We identified miR-29a and PSAT1 as new candidates to regulate immunosuppressive activity mediated by MSCs