• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 275
  • 99
  • 84
  • 39
  • 28
  • 19
  • 10
  • 4
  • 3
  • 2
  • 2
  • 2
  • 2
  • 2
  • 1
  • Tagged with
  • 694
  • 123
  • 118
  • 98
  • 94
  • 92
  • 72
  • 68
  • 61
  • 54
  • 51
  • 48
  • 41
  • 40
  • 39
  • About
  • 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

Functionality and efficiency improvement of miRCheck, a popular program for microRNA structure prediction

Bandyopadhyay, Parika 16 February 2015 (has links)
Plant and animals both contain non-coding small RNAs that play important roles in their growth, development and responses to biotic and abiotic stresses. MicroRNAs are short (20-24nt), endogenously expressed, and a well characterized class of small RNAs, which are derived from processing longer, hairpin-like precursors. Discovery of most miRNAs relies upon either of two methods: i) molecular cloning of small RNAs or ii) prediction of miRNA genes based on conserved sequences, and secondary structures of known miRNAs using computational tools. miRCheck is a popular computational tool chain comprised of various Perl scripts for identifying and profiling plant miRNA genes. The program serves two purposes: 1. Identifying miRNA homologs in target genomic or cDNA sequences using a given small RNA library, 2. Searching for all potential miRNA precursor loci across the target genome based on evolutionarily-conserved structural features without any reference small RNA library to compare with. miRCheck builds upon several popular tools like patscan, RNAfold, einverted, and connects them to provide a complete tool chain for identifying miRNAs. Although miRCheck is a very well designed tool chain, it still has a few issues that need to be addressed to enhance its functionality and efficiency. This work analyzes the working mechanism of miRCheck, proposes some methods to enhance its efficiency and functionality, and implements those in a modified tool chain, py-miRCheck, in Python. To process a long genome sequence, miRCheck looks at small segments and serially evaluates them leading to long run times. Even in a high performance computing node, it takes days to process a standard sized reference genome obtained from NCBI repository. It highlights the inefficiency in the program. On the functionality side, there are several issues that need to be addressed for usability improvements: i) lack of parameterized design, ii) procedural design, iii) lack of GUI interface for running the tool chain, and iv) deployment-related problems. In this work, I address all these areas and also parallelize the tool chain to improve its efficiency by over a factor of 3. I also provide a Django-based prototype web front end to submit queries on a genome sequence. In summary, this work improves the usability of this tool chain to a great extent. / text
2

Hairpins in a Haystack: recognizing microRNA precursors in comparative genomics data

Hertel, Jana, Stadler, Peter F. 06 November 2018 (has links)
Recently, genome-wide surveys for non-coding RNAs have provided evidence for tens of thousands of previously undescribed evolutionary conserved RNAs with distinctive secondary structures. The annotation of these putative ncRNAs, however, remains a difficult problem. Here we describe an SVM-based approach that, in conjunction with a non-stringent filter for consensus secondary structures, is capable of efficiently recognizing microRNA precursors in multiple sequence alignments. The software was applied to recent genome-wide RNAz surveys of mammals, urochordates, and nematodes.
3

Structural profiles of human miRNA families from pairwise clustering

Kaczkowski, Bogumił, Torarinsson, Elfar, Reiche, Kristin, Havgaard, Jakob Hull, Stadler, Peter F., Gorodkin, Jan 06 November 2018 (has links)
MicroRNAs (miRNAs) are a group of small, ∼21 nt long, riboreg-ulators inhibiting gene expression at a post-transcriptional level. Their most distinctive structural feature is the foldback hairpin of their precursor pre-miRNAs. Even though each pre-miRNA deposited in miRBase has its secondary structure already predicted, little is known about the patterns of structural conservation among pre-miRNAs. We address this issue by clustering the human pre-miRNA sequences based on pairwise, sequence and secondary structure alignment using FOLDALIGN, followed by global multiple alignment of obtained clusters by WAR. As a result, the common secondary structure was successfully determined for four FOLDALIGN clusters: the RF00027 structural family of the Rfam database and three clusters with previously undescribed consensus structures.
4

Optimisation of expressed RNA interference mimics using predicted stem length

Van den Berg, Fiona Taylor January 2016 (has links)
A thesis submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Doctor of Philosophy. Johannesburg, 2016. / Primary microRNA (pri-miRNA) mimics have been shown to mediate effective gene silencing and are well-suited for therapeutic applications. Pri-miRNA mimics, like natural pri-miRNA, are processed in the endogenous microRNA (miRNA) biogenesis pathway. Elements of the secondary RNA structure are crucial for processing by the Drosha-DGCR8 microprocessor, including a basal stem of - 11 bp. However, structural variation is common and the exact determinants of pri-miRNA processing have been elusive. The aim of this project were to explore the use of natural pri-miRNAs with exceptional basal stem in the design of correspondingmimics and to identify optimal stem features.[Abbreviated Abstract. Open document to view full version] / LG2017
5

MicroRNA-205 Involvement in Cutaneous Melanoma

Rees, Evan 09 July 2012 (has links)
Cutaneous melanoma is an increasingly common aggressive malignancy. The molecular mechanisms responsible for melanoma’s initiation and progression are still unclear, but new evidence suggests microRNAs (miRNAs) may be involved. MicroRNAs are small non-coding RNAs that have been shown to act as either oncogenes or tumour suppressors. These short, ~22 nucleotide long, single stranded RNA molecules regulate gene expression post-transcriptionally, through complementary binding to target messenger RNA (mRNA), and mediate mRNA degradation and translational repression. Our laboratory has previously shown that miRNA expression levels are altered through the different stages of melanoma tumourigenesis and has identified numerous significantly dysregulated miRNAs. miR-205 expression is significantly decreased in both primary and metastatic melanoma. Because of this decrease in miR-205 level with increasing cancer aggressiveness, we originally hypothesized that miR-205 may act as a tumour suppressor in melanoma. Unexpectedly, miR-205 re-expression in metastatic melanoma cells has shown oncogenetic potential. Through functional assays, we determined that miR-205 plays a primary role in promoting cellular migration and invasion, and in repressing adhesion. A gene expression analysis was conducted and the target prediction algorithm TargetScan was utilized to determine potential mRNA targets for miR-205. CADM1, PTPRJ and SHIP2 were three of the targets investigated, because of their known functional role in migration and cellular adhesion. CADM1 and PTPRJ were both verified to be directly targeted by miR-205 in an in vitro melanoma system using a luciferase reporter assay. In summary, we have demonstrated a surprising functional role for miR-205 in melanoma. The re-expression of miR-205 promotes malignant phenotypes and therefore is functioning with oncogenic potential within our metastatic melanoma cell culture system. / Thesis (Master, Pathology & Molecular Medicine) -- Queen's University, 2012-07-09 12:32:35.235
6

Role of Microornas in Tumroigenesis and their Modulation by Versican 3' Untranslated Region

Lee, Daniel Yen-Hong 15 September 2011 (has links)
MicroRNA is a single-stranded RNA molecule of about 22 nucleotides in length and is expressed endogenously. It functions as a gene regulator by pairing imperfectly with 3’ untranslated region (3’UTR) of target mRNAs, leading to translational inhibition. MicroRNA is implicated in many regulatory pathways and hence affects various cellular activities. In the development of cancer, genetic alterations occurred at miRNA locus and its expression level is dysregulated in various cancers versus normal tissue counterparts. It is thus important to find the targets of dysregulated microRNAs contributing to progression of cancer. To facilitate long term functional studies, a microRNA expression construct with unique futures was generated. Stable expression of miR-378 enhanced cell survival, reduced caspase-3 activity, and promoted tumor growth and angiogenesis. By algorithmic predictions and proteomic analysis, two tumor suppressors, SuFu and Fus-1, were found to be translationally regulated by miR-378. Target validation was confirmed by co-transfection experiments and luciferase activity assays, reassuring its oncogenic role by regulating two tumor suppressor genes simultaneously. Conversely, microRNA can also function as a tumor suppressor by modulating expression of Versican, an extracellular matrix protein known to facilitate tumorigenesis and angiogenesis. By a novel PCR method, more than one microRNA were found to bind to Versican 3’UTR. iii Among these microRNAs, targeting of Versican and Fibronectin by miR199a-3p was validated. Expression of a fragment of Versican 3’UTR was expected to antagonize the function of miR-199a-3p. Stable expression of Versican 3’UTR resulted change in cell morphology and increased cell-cell adhesion. Analysis of primary tissues from transgenic mice expressing versican 3’UTR showed an increase expression of Versican and Fibronectin, and organ adhesion was found between liver and its surrounding tissues. In addition, 3’UTR also modulated the level of miR-199a-3p and miR-136, alleviating translation of negative cell cycle regulators, PTEN and Rb1. This resulted in reduced cell proliferation and hence diminished tumor growth. These findings suggest a role of microRNA in tumor growth, providing a valuable target for therapeutic intervention.
7

Role of Microornas in Tumroigenesis and their Modulation by Versican 3' Untranslated Region

Lee, Daniel Yen-Hong 15 September 2011 (has links)
MicroRNA is a single-stranded RNA molecule of about 22 nucleotides in length and is expressed endogenously. It functions as a gene regulator by pairing imperfectly with 3’ untranslated region (3’UTR) of target mRNAs, leading to translational inhibition. MicroRNA is implicated in many regulatory pathways and hence affects various cellular activities. In the development of cancer, genetic alterations occurred at miRNA locus and its expression level is dysregulated in various cancers versus normal tissue counterparts. It is thus important to find the targets of dysregulated microRNAs contributing to progression of cancer. To facilitate long term functional studies, a microRNA expression construct with unique futures was generated. Stable expression of miR-378 enhanced cell survival, reduced caspase-3 activity, and promoted tumor growth and angiogenesis. By algorithmic predictions and proteomic analysis, two tumor suppressors, SuFu and Fus-1, were found to be translationally regulated by miR-378. Target validation was confirmed by co-transfection experiments and luciferase activity assays, reassuring its oncogenic role by regulating two tumor suppressor genes simultaneously. Conversely, microRNA can also function as a tumor suppressor by modulating expression of Versican, an extracellular matrix protein known to facilitate tumorigenesis and angiogenesis. By a novel PCR method, more than one microRNA were found to bind to Versican 3’UTR. iii Among these microRNAs, targeting of Versican and Fibronectin by miR199a-3p was validated. Expression of a fragment of Versican 3’UTR was expected to antagonize the function of miR-199a-3p. Stable expression of Versican 3’UTR resulted change in cell morphology and increased cell-cell adhesion. Analysis of primary tissues from transgenic mice expressing versican 3’UTR showed an increase expression of Versican and Fibronectin, and organ adhesion was found between liver and its surrounding tissues. In addition, 3’UTR also modulated the level of miR-199a-3p and miR-136, alleviating translation of negative cell cycle regulators, PTEN and Rb1. This resulted in reduced cell proliferation and hence diminished tumor growth. These findings suggest a role of microRNA in tumor growth, providing a valuable target for therapeutic intervention.
8

MicroRNAs as Prognostic Biomarkers in Prostate Cancer

Gordanpour, Aida 12 December 2012 (has links)
Prostate cancer, one of the most common cancers among men, can be relatively harmless or extremely aggressive. The most widely used biomarker for the disease, the PSA test, is not independently diagnostic or prognostic of prostate cancer. One of the main challenges of prostate cancer research is to find reliable and effective prognostic biomarkers that will predict cancer recurrence following surgery, in order to identify clinically significant prostate cancer and improve management of the disease. In recent years, microRNAs (miRNAs) have been identified as master regulators of cellular processes, and dysregulated miRNAs have been associated with cancer development and progression. The intent of my PhD research program was to uncover novel miRNAs that contribute to prostate cancer pathogenesis in order to assess their potential as predictors of clinical progression. By analyzing a large cohort of primary prostate cancer samples, we have discovered that microRNA-221 (miR-221) is associated with metastasis and biochemical recurrence in prostate cancer, and is downregulated in TMPRSS2:ERG fusion gene- positive tumors. In addition, we have determined that microRNA-182 (miR-182) is overexpressed in prostate cancer and is associated with increased metastasis and clinical progression by targeting a tumors suppressor Forkhead box O1 (FOXO1). Overall, this work introduces novel candidate miRNA genes and downstream targets that are aberrantly expressed in more aggressive prostate cancer, and presents a potentially significant role for miRNAs as prognostic biomarkers that are associated with clinical progression, and perhaps aids in defining how miRNAs might one day serve as anti-cancer therapeutic agents.
9

Investigation of the molecular mechanisms controlling the function of human natural regulatory T cells

Fayyad-Kazan, Hussein 07 December 2010 (has links)
Regulatory T cells (Tregs) are a subpopulation of T cells with immuno-suppressive properties. Tregs play a key role in immune response regulation and tolerance to antigens, thereby preventing autoimmunity, and may be partly responsible for the lack of an appropriate immune response against tumor cells. However, a human microRNA (miR) Treg signature has not been described yet. We investigated human natural Tregs and identified a signature composed of five microRNAs (-21, -31, -125a, -181c and -374). Among those, two were considerably under-expressed (miR-31 and miR-125a). We identified a functional target sequence for miR-31 in the 3’ untranslated region (3’ UTR) of FOXP3 mRNA. Using lentiviral transduction of fresh cord blood T cells, we demonstrated that miR-31 and miR-21 had opposite effects on FOXP3 expression. We showed that miR-31 negatively regulates FOXP3 expression by binding directly to its potential target site in the 3’ UTR of FOXP3 mRNA. We next demonstrated that miR-21 acted as a positive, though indirect, regulator of FOXP3 expression. Recent reports have shown that histone deacetylase inhibitors increased FOXP3 expression in T cells. We therefore decided to investigate in non-Treg CD4-positive cells, the mechanisms by which an aspecific opening of the chromatin could lead to an increased FOXP3 expression. We focused on the binding of potentially activating transcription factors to the promoter region of FOXP3 and on modifications in the five miRs constituting the Treg signature. Valproate treatment induced binding of Ets-1 and Ets-2 transcription factors to the FOXP3 promoter and acted positively on its expression, by increasing the acetylation of histone H4 lysines. Valproate treatment also induced the acquisition of the miRs of Treg signature. To elucidate whether the changes in the miRs expression could be due to the increased FOXP3 expression, we transduced these non-Tregs with a FOXP3 lentiviral expression vector, and found no changes in miRs expression. Therefore, the modification in their miR expression profile is not due to an increased expression of FOXP3 but directly results from histone deacetylase inhibition. Rather, the increased FOXP3 expression results from the additive effects of Ets factors binding and the change in the expression level of miR-21 and miR-31. These data, by allowing a better understanding of the molecular phenomena underlying the number and function of Tregs, could open the door to novel therapeutic approaches in cancer immunotherapy and treatment of autoimmune disorders.
10

MicroRNAs as Prognostic Biomarkers in Prostate Cancer

Gordanpour, Aida 12 December 2012 (has links)
Prostate cancer, one of the most common cancers among men, can be relatively harmless or extremely aggressive. The most widely used biomarker for the disease, the PSA test, is not independently diagnostic or prognostic of prostate cancer. One of the main challenges of prostate cancer research is to find reliable and effective prognostic biomarkers that will predict cancer recurrence following surgery, in order to identify clinically significant prostate cancer and improve management of the disease. In recent years, microRNAs (miRNAs) have been identified as master regulators of cellular processes, and dysregulated miRNAs have been associated with cancer development and progression. The intent of my PhD research program was to uncover novel miRNAs that contribute to prostate cancer pathogenesis in order to assess their potential as predictors of clinical progression. By analyzing a large cohort of primary prostate cancer samples, we have discovered that microRNA-221 (miR-221) is associated with metastasis and biochemical recurrence in prostate cancer, and is downregulated in TMPRSS2:ERG fusion gene- positive tumors. In addition, we have determined that microRNA-182 (miR-182) is overexpressed in prostate cancer and is associated with increased metastasis and clinical progression by targeting a tumors suppressor Forkhead box O1 (FOXO1). Overall, this work introduces novel candidate miRNA genes and downstream targets that are aberrantly expressed in more aggressive prostate cancer, and presents a potentially significant role for miRNAs as prognostic biomarkers that are associated with clinical progression, and perhaps aids in defining how miRNAs might one day serve as anti-cancer therapeutic agents.

Page generated in 0.1252 seconds