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• The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

#### Computational Prediction of Target Genes of MicroRNAs

MicroRNAs (miRNAs) are a class of short (21-25 nt) non-coding endogenous RNAs that mediate the expression of their direct target genes post-transcriptionally. The goal of this thesis is to identify the target genes of miRNAs using computational methods. The most popular computational target prediction methods rely on sequence based determinants to predict targets. However, these determinants are neither sufficient nor necessary to identify functional target sites, and commonly ignore the cellular conditions in which miRNAs interact with their targets \emph{in vivo}. Since miRNAs activity reduces the steady-state abundance of mRNA targets, the main goal of this thesis is to augment large scale gene expression profiles as a supplement to sequence-based computational miRNA target prediction techniques. We develop two computational miRNA target prediction methods: InMiR and BayMiR; in addition, we study the interaction between miRNAs and lncRNAs using long RNA expression data. InMiR is a computational method that predicts the targets of intronic miRNAs based on the expression profiles of their host genes across a large number of datasets. InMiR can also predict which host genes have expression profiles that are good surrogates for those of their intronic miRNAs. Host genes that InMiR predicts are bad surrogates contain significantly more miRNA target sites in their 3 UTRs and are significantly more likely to have predicted Pol II-III promoters in their introns. We also develop BayMiR that scores miRNA-mRNA pairs based on the endogenous footprint of miRNAs on gene expression in a genome-wide scale. BayMiR provides an endogenous target repression" index, that identifies the contribution of each miRNA in repressing a target gene in presence of other targeting miRNAs. This thesis also addresses the interactions between miRNAs and lncRNAs. Our analysis on expression abundance of long RNA transcripts (mRNA and lncRNA) shows that the lncRNA target set of some miRNAs have relatively low abundance in the tissues that these miRNAs are highly active. We also found lncRNAs and mRNAs that shared many targeting miRNAs are significantly positively correlated, indicating that these set of highly expressed lncRNAs may act as miRNA sponges to promote mRNA regulation.
2

#### Computational Prediction of Target Genes of MicroRNAs

MicroRNAs (miRNAs) are a class of short (21-25 nt) non-coding endogenous RNAs that mediate the expression of their direct target genes post-transcriptionally. The goal of this thesis is to identify the target genes of miRNAs using computational methods. The most popular computational target prediction methods rely on sequence based determinants to predict targets. However, these determinants are neither sufficient nor necessary to identify functional target sites, and commonly ignore the cellular conditions in which miRNAs interact with their targets \emph{in vivo}. Since miRNAs activity reduces the steady-state abundance of mRNA targets, the main goal of this thesis is to augment large scale gene expression profiles as a supplement to sequence-based computational miRNA target prediction techniques. We develop two computational miRNA target prediction methods: InMiR and BayMiR; in addition, we study the interaction between miRNAs and lncRNAs using long RNA expression data. InMiR is a computational method that predicts the targets of intronic miRNAs based on the expression profiles of their host genes across a large number of datasets. InMiR can also predict which host genes have expression profiles that are good surrogates for those of their intronic miRNAs. Host genes that InMiR predicts are bad surrogates contain significantly more miRNA target sites in their 3 UTRs and are significantly more likely to have predicted Pol II-III promoters in their introns. We also develop BayMiR that scores miRNA-mRNA pairs based on the endogenous footprint of miRNAs on gene expression in a genome-wide scale. BayMiR provides an endogenous target repression" index, that identifies the contribution of each miRNA in repressing a target gene in presence of other targeting miRNAs. This thesis also addresses the interactions between miRNAs and lncRNAs. Our analysis on expression abundance of long RNA transcripts (mRNA and lncRNA) shows that the lncRNA target set of some miRNAs have relatively low abundance in the tissues that these miRNAs are highly active. We also found lncRNAs and mRNAs that shared many targeting miRNAs are significantly positively correlated, indicating that these set of highly expressed lncRNAs may act as miRNA sponges to promote mRNA regulation.
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#### Análise de miRNoma em sangue periférico de indivíduos com obesidade e resistência à insulina / Analysis of miRNA in peripheral blood of the individual with obesity and insulin resistance

Braga, Aécio Assunção 20 December 2018 (has links)
6

#### Análise de miRNoma em sangue periférico de indivíduos com obesidade e resistência à insulina / Analysis of miRNA in peripheral blood of the individual with obesity and insulin resistance

Aécio Assunção Braga 20 December 2018 (has links)
7

#### miRNA functions in pluripotency and spermatogenesis

Smorag, Lukasz 18 October 2012 (has links)
No description available.
8

#### Identification of miRNAs and their target genes in stem cell derived cardiomyocytes

Jantscher, Yvonne January 2011 (has links)
Stem cell research, especially the one dealing with human embryonic stem cells, is a major topic nowadays. In the last few years studies about human embryonic stem cell derived cardiomyocytes highlighted the importance of those, as their characteristics are almost identical as of the cardiomyocytes in the heart (i.e. the contraction of those cells). The studies concentrate on the ability of using cardiomyocytes in the drug development for cardiac diseases or in regenerative medicine and cell replacement therapies. In contrast some researchers concentrate on microRNAs (miRNAs) as regulators in the development of cardiomyocytes. This study combines both research topics as it deals with stem cells and miRNAs (as well as their target mRNAs). A main objective is to find differentially expressed genes by using Significance Analysis of Microarrays (SAM) as method. Furthermore miRNA target prediction is applied and the identified targets are compared with the ones found by SAM. With an intersection approach we derived 41 targets of up-regulated miRNAs and 25 targets of down-regulated miRNAs, which can be the basis for further studies (i.e. knock-out experiments).
9

#### Identification of novel microRNAs as potential biomarkers for the early diagnosis of ovarian cancer using an in-silico approach

Zahra, Latib January 2019 (has links)
Philosophiae Doctor - PhD / Ovarian cancer (OC) is the most fatal gynaecologic malignancy that is generally diagnosed in the advanced stages, resulting in a low survival rate of about 40%. This emphasizes the need to identify a biomarker that can allow for accurate diagnosis at stage I. MicroRNAs (miRNAs) are appealing as biomarkers due to their stability, non-invasiveness, and differential expression in tumour tissue compared to healthy tissue. Since they are non-coding, their biological functions can be uncovered by examining their target genes and thus identifying their regulatory pathways and processes. This study aimed to identify miRNAs and genes as candidate biomarkers for early stage OC diagnosis, through two distinct in silico approaches. The first pipeline was based on sequence similarity between miRNAs with a proven mechanism in OC and miRNAs with no known role. This resulted in 9 candidate miRNAs, that have not been previously implicated in OC, that showed 90-99% similarity to a miRNA involved in OC. Following a series of in silico experimentations, it was uncovered that these miRNAs share 12 gene targets that are expressed in the ovary and also have proven implications in the disease. Since the miRNAs target genes contribute to OC onset and progression, it strengthens the notion that the miRNAs may be dysregulated as well. Using TCGA, the second pipeline involved analysing patient clinical data along with implementing statistical measures to isolate miRNAs and genes with high expression in OC. This resulted in 26 miRNAs and 25 genes being shortlisted as the potential candidates for OC management. It was also noted that targeting interactions occur between 15 miRNAs and 16 genes identified through this pipeline. In total, 35 miRNAs and 37 genes were identified from both pipelines.
10

#### Investigation of key non-coding and coding genes in cutaneous melanomagenesis

Xu, Yan January 2011 (has links)
Cutaneous melanoma is associated with significant morbidity and mortality representing the most significant cutaneous malignancy. As it is known that early diagnosis and treatment are the most efficient approaches to cure cutaneous melanoma, an improved understanding of the molecular pathogenesis of melanoma and exploration of more reliable molecular biomarkers are particularly essential. Two different types of molecular biomarker for melanoma have been investigated in this thesis. microRNAs (miRNAs) are single-stranded RNA molecules of 20-23 nucleotides in length that are found in both animal and plant cells. miRNAs are involved in the RNA interference (RNAi) machinery to regulate gene expression posttranscriptionally. miRNAs have important roles in cancer: by controlling the expression level of their target genes they can affect cell signalling pathways and have been shown to have both prognostic and therapeutic potential. Importantly for melanoma research, reproducible miRNA expression profiles from formalin-fixed paraffin-embedded (FFPE) tissues can be obtained that are comparable to those from fresh-frozen samples. The aims of the miRNA project were: first, to identify a melanoma-specific miRNA expression profile; secondly, to investigate roles of some of the melanoma-specific miRNAs identified in melanomagenesis. Using miRNA microarray on FFPE samples, I obtained a melanoma-specific miRNA expression profile. 9 of these differentially expressed miRNAs between benign naevi and melanomas (7 downregulated, 2 upregulated in malignancies) were verified by qRT-PCR and the functions of four of these miRNAs were studied. Ectopic overexpression of miR- 200c and miR-205 in A375 melanoma cells inhibited colony forming ability in methylcellulose, an in vitro surrogate assay for tumourigenicity. Moreover, elevation of miR-200c resulted in increased expression levels of E-cadherin through negative regulation of the zinc finger E-box-binding homeobox 2 (ZEB2) gene. Ectopic overexpression of miR-211 in A375 melanoma cells repressed both colony formation in methylcellulose and migratory ability in matrigel, an in vitro surrogate assay for invasiveness. These findings indicate that miR-200c, miR-205 and miR-211 act as tumour suppressors in melanomagenesis. The second biomarker investigated, mutated BRAF, has been seen in 50-70% of spontaneous cutaneous melanoma. The commonest mutation in melanoma is a glutamic acid for valine substitution at position 600 (V600E). Oncogenic BRAF controls many aspects of melanoma cell biology. The aim of this part of the work was: firstly, to study BRAF V600E mutation status in our melanoma tissue microarray (TMA) panel; secondly, to correlate this mutation to various clinicopathological features and evaluate its prognostic value through statistical analyses. BRAF V600E mutations were seen in 20% of the primary and 69% of the metastatic melanomas, respectively. More BRAF V600E mutations were seen in males relative to females. The mutation was also related to cell pigmentation, but not to age, ulceration or solar elastosis. Melanoma patients with the BRAF V600E mutation relapse earlier than patients without this mutation. However, no significant association between the BRAF V600E mutation and overall survival and melanoma specific survival was found.

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