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Delivery Of Microrna With Cxcr4-Targeted Nanoparticles In Metastatic Cancer Treatment, Ying Xie

Theses & Dissertations

Metastasis is the main contributor to cancer-associated deaths. Inhibition of CXCR4 emerged as one promising approach in metastatic cancer therapy. MiRNAs represent a new class of therapeutics for cancer treatment through RNA interference-mediated gene silencing. Polymeric CXCR4 antagonist (PCX) is a dual-functional polycation to inhibit CXCR4 and deliver nucleic acids. This dissertation hypothesized that blockade of CXCR4 by PCX combined with delivery of miRNA cooperatively enhances metastatic cancer therapy.

In chapter 1, an overview of CXCR4 inhibition, miRNA delivery and CXCR4 targeted nanomedicine in cancer therapy is given.

Chapter 2 reports that PCX can effectively deliver miR-200c mimic and that …

Sequence-Specific Extracellular Micrornas Activate Tlr7, Niming Wu

Theses & Dissertations

Toll-like receptors (TLRs) play an important role in the innate immune system. Emerging evidence shows that TLRs, especially endosomal TLRs, can participate in CNS diseases by increasing the production of proinflammatory cytokines via recognition of microRNAs (miRNAs), however which of the miRNAs are able to activate signaling and whether specific sequence motifs are involved remains incompletely defined. Here we found that numerous miRNAs induced TNF-a production across multiple myeloid cell types, including microglia, and that this effect was abolished in cells deficient of TLR7. In particular, miR-20a-5p and miR-148b-3p preferentially stimulate cytokine secretion compared to miR-20b-5p and miR-148a-3p, respectively, despite …

Local Delivery Of Mesenchymal Stem Cells Expressing Osteogenesis-Inducing Microrna For Bone Tissue Engineering Applications, Marco Antonio Arriaga

Theses and Dissertations

Bone is capable of regenerating autonomously when the injury is small (< 2.5 cm), however, large (> 2.5 cm) or insufficiently vascularized defects require intervention to repair. The overall goal of this project is to contribute towards the development of novel strategies to aid bone tissue regeneration by delivering mesenchymal stem cells expressing microRNAs that induce expression of the runt-related transcription factor 2 (RUNX2). It was determined that porous polycaprolactone (PCL) scaffolds fabricated to have a higher surface area to volume ratio (SVR) (> 80) compared to lower SVR (< 80) were hydrolyzed at a higher rate. Scaffolds fabricated with 80 vol. %/300–500 µm porogen were optimal for cell colonization as higher absorbance of metabolized MTT was detected compared to other scaffold types. From the subset of 5 miRNAs tested, miRNA-26a, miRNA-196 and miRNA-218 demonstrated higher upregulation of RUNX2 gene expression and calcium mineralization and thus, are promising candidates for bone tissue regeneration.

Gq Noncanonical Roles In Translational Regulation, Brett Demarco

Electronic Theses and Dissertations

This study investigates protein nucleic acid interactions, focusing on G-quadruplex (GQ) forming DNA/RNA in human disease. GQ structures are formed in DNA/RNA, when four guanine residues form planar tetrads stabilized by Hoogsteen base pairing, that stack forming a GQ structure stabilized by potassium ions. These GQ structures are targeted by the arginine glycine-glycine (RGG) RNA-binding domain. Fragile X mental retardation protein (FMRP), a translation regulator protein implicated in the fragile X syndrome, has an RGG domain and has been previously shown to interact with neuronal GQ forming messenger RNA (mRNA). We have investigated three neuronal FMRP mRNA targets that we …

Microrna Functions In Uv-Induced Cutaneous Squamous Cell Carcinoma, Tran Nguyen

Dissertations & Theses (Open Access)

Cutaneous squamous cell carcinoma (cuSCC) is the second most common skin cancer, for which long term UV exposure and chronic wounding are the dominant risk factors. Despite these clinically established connections, little is understood about the early molecular response of human skin to UV exposure and its connection to acute wounding and cuSCC. Thus, our goal is to find common and specific signatures driven by UV-exposure and wounding as a means of developing new approaches for treating and preventing cuSCC.

Here, we perform integrated analyses of RNA-seq and miR-seq on 3 datasets: (1) UV-unexposed and acute UV-exposed human skin, (2) …

Cooperative Regulation Of Translational Repression By Fmrp And The Mirna Pathway, Navneeta Kaul

Electronic Theses and Dissertations

Fragile X syndrome (FXS) is the most common inherited monogenic cause of intellectual disability. FXS patients exhibit social and language deficits, hyperactivity, seizures, growth abnormalities, macroorchidism, anxiety, and epilepsy. FXS is caused by the transcriptional silencing of the fragile X mental retardation gene 1 (Fmr1), resulting in the loss of the fragile X mental retardation protein (FMRP). FMRP is a selective mRNA binding protein that plays a role in translation repression. Studies suggest that FMRP utilizes the miRNA pathway to repress translation of its target mRNAs through an unknown mechanism. The aim of my thesis is to investigate …

Genomic Approaches To Identify Important Traits In Avian Species, Bhuwan Khatri

Graduate Theses and Dissertations

This dissertation focusses on identifying different molecular markers that have impact on overall poultry production. Chapter one reviews microRNA (miRNA), copy number variation (CNV) and single nucleotide polymorphism (SNP) as markers suggested in different avian species by various studies. It reviews modern genomic approaches that are employed for next generation sequencing data analysis and verification.

Chapter two seeks to identify and validate the muscle specific miRNAs in the breast muscle of modern broilers and its foundational chicken line. Small RNA sequencing was performed to identify differentially expressed mature miRNAs in the breast muscles of these two chicken lines. Results showed …

Computational Analysis Of Genomic Variants Affecting Predicted Microrna:Target Interactions In Prostate Cancer., Angélica Paola Hernández Pérez

KGI Theses and Dissertations

Prostate cancer (PCa) is the most common cancer of men in the United States and is third only to lung and colon as a cause of cancer death. Clinical behavior of the disease is variable and the combination of prostate-specific antigen (PSA) screening and Gleason score staging are currently the best available molecular and pathology tools to predict outcomes. Cancer biology research establishes microRNAs (miRNAs) as key molecular components in both normal and pathological states. Thus, elucidating miRNAs perturbed by genomic alterations will expand our understanding of the molecular taxonomy of PCa with the aim to complement current practices in …

Developing More Specific Mirna Biogenesis Inhibitors To Get Effective Regulation Of Mirnas, Umesh Bhattarai

Chemistry and Chemical Biology ETDs

MicroRNAs (miRNAs) are short (~ 22 nucleotides long) noncoding RNAs that regulate gene expression post-transcriptionally. They control the expression of various genes that are crucial for cellular function, development and human diseases. Tools to regulate the level and function of miRNAs facilitate the studies of their functions and have therapeutic applications. In my thesis, I developed a newly customizable miRNA biogenesis inhibitor to regulate miRNAs.

Antisense oligonucleotides (ASOs) have been used to regulate miRNA through controlling their production or function. Although commonly used due to the fact that they are easy to design, several limitations exist for ASOs including serious …

Inference And Analysis Of Multilayered Mirna-Mediated Networks In Cancer, Duc Do

Dissertations (1934 -)

MicroRNAs (miRNAs) are small noncoding transcripts that can regulate gene expression, thereby controlling diverse biological processes. Aberrant disruptions of miRNA expression and their interactions with other biological agents (e.g., coding and noncoding transcripts) have been associated with several types of cancer. The goal of this dissertation is to use multidimensional genomic data to model two different gene regulation mechanisms by miRNAs in cancer. This dissertation results from two research projects. The first project investigates a miRNA-mediated gene regulation mechanism called competing endogenous RNA (ceRNA) interactions, which suggests that some transcripts can indirectly regulate one another's activity through their interactions with …

Investigating Circulatory Microrna Expression Profiles In Egyptian Patients With Hcv Induced Hepatocellular Carcinoma, Amany Al Anany

Theses and Dissertations

Hepatitis C virus (HCV) infection is a serious health challenge affecting over 185 million individuals globally. Egypt has the highest rate for chronic HCV infection worldwide. Recent studies have shown that from 10%-30% of HCV infected individuals would progress to more deteriorating conditions such as cirrhosis and/or hepatocellular carcinoma (HCC). Current biomarkers for HCC diagnosis are lacking both sensitivity and specificity. As a result there is demand to develop reliable biomarkers that are sensitive, specific and non-invasive for early diagnosis and rapid intervention of HCC to increase the survival rate of patients. Recently, circulatory miRNAs have drawn great attention as …

Microrna Expression And Disease Correlation In A Hispanic Lupus Cohort, Thandiwe Jere

Theses & Dissertations

Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease with varying clinical presentation and severity in different ethnicities/races. Micro-RNAs (miRNAs) modulate the immune system, and there is a growing interest in their role in SLE pathogenesis and disease presentation. Studies on miRNAs expression in SLE have been done in Caucasians and Asians but no comprehensive profiling has been done in Hispanics. This cross-sectional study of a Hispanic cohort of SLE patients (n =185) and healthy controls (HC) (n =185) from the Dominican Republic determined the expression of 10 selected miRNAs and their correlation to inflammatory markers and auto-antibody production in …

Comprehensive Evaluation Of The Anti-Fibrogenic Effect Of Astaxanthin In Hepatic Stellate Cells, Minkyung Bae

Doctoral Dissertations

'Archival abstract submitted'

Circulating Microrna Following High Intensity Interval Cycling With And Without Post-Exercise Nutrient Consumption, Jeremy Via

Masters Theses, 2010-2019

Introduction: MicroRNA (miRNA) are small, non-coding RNA that act post-transcriptionally to regulate gene expression. miRNA levels are modulated by acute aerobic exercise, yet little is known about how miRNA levels may change in response to high-intensity interval exercise. Further, almost nothing is known about the impact of post-exercise nutrition (carbohydrate and/or protein) on miRNA levels. Thus, the purpose of this study is to examine the effects of high-intensity interval cycling and different post-exercise nutrients on ci-miRNA levels. Methods: Nine recreationally active males (age 21.9 ± 2.0yrs; VO_2max 49.6 ± 4.0mL/kg/min) competed three trials, each including identical exercise protocols. Protocol …

Regulation Of Interactions Between Sap-Feeding Insects And Their Obligate Endosymbionts, Honglin Feng

Open Access Dissertations

Many insects cultivate obligate endosymbionts for nutrition. Genomic analyses, coupled with physiological evidence demonstrate that insects and their obligate endosymbionts are intimately integrated in biosynthesis of essential nutrients, including essential amino acids. However, the mechanisms that underlie regulation of host/endosymbiont integrations remain elusive. Using sap-feeding insects, I investigated the role of amino acid transporters and microRNAs in host/endosymbiont integrations. In the first data chapter in aphids, I determined the localization of aphid glutamine transporter ApGLNT1 and another amino acid transporter ACYPI008971. ApGLNT1 specifically localizes at the plasma membrane of bacteriocytes, the aphid specialized cells harboring the endosymbiont Buchnera aphidicola. ACYPI008971 …

Identification Of Regulatory Mirnas Associated With Ethanol-Induced Microglial Activation Using Integrated Proteomic And Transcriptomic Approaches, Brandi Jo Cook

USF Tampa Graduate Theses and Dissertations

Chronic consumption of, and acute intoxication from, alcohol can have profound effects on the functional integrity of the central nervous system (CNS). The resident immunomodulatory cells of the CNS, microglia, provide signaling factors with both pro- and anti-inflammatory effects for protection. Microglial activation ranges through a multiplex of phases, of which have yet to be defined when induced by exposure to alcohol, and how the activation impacts surrounding cells. Exposure of alcohol has been revealed to induce an immune response in microglia, which can exhibit characteristics unique to a pro-inflammatory response depending on dose and time of alcohol exposure. To …

Post-Transcriptional Regulation Of Myeloid Cell Leukemia 1 In Cancers, Jia Cui

All ETDs from UAB

Apoptosis, a highly regulated process of programmed cell death, is essential for maintaining normal tissue homeostasis. Myeloid cell leukemia 1 (MCL1), an anti-apoptotic BCL-2 family protein, lies at the center of apoptosis regulation. Overexpression of MCL1 has been identified as a key contributor to tumorigenesis and further enables resistance to anti-cancer chemotherapies and radiation. Due to the critical roles of MCL1 in cancer, it is essential to understand the regulatory mechanisms of MCL1 expression in cells. Previous studies have detailed how MCL1 expression is controlled by multiple mechanisms. However, characterization of the post-transcriptional regulation of MCL1 mRNA has been poorly …

Chemically And Biologically Responsive Nanoparticle Systems For Biomarker Detection And Combination Cancer Therapy, Neil M. Robertson

Legacy Theses & Dissertations (2009 - 2024)

The uniqueness and expression of miRNAs as biomarkers in certain cancers has the potential to radically alter the detection, and therefore the treatment, of the disease. Not only are current detection methods time consuming, and not sensitive enough for biomedical applications, but these small RNAs have yet to be fully utilized in treatment. By utilizing different nanomaterials we aimed to create novel nanodevices for the early, sensitive and specific detection of these biomarkers in a minimally invasive way and develop dual drug releasing nanoparticles, which are entirely controllable, to aid in the treatment of resistant cancer phenotypes.

Technology Development For Detection Of Circulating Disease Biomarkers From Liquid Biopsies Using Multifunctional Nanomaterials, Mustafa Balcioglu

Legacy Theses & Dissertations (2009 - 2024)

Despite the advance health care, devastating health conditions such as cancer and infectious diseases that affect populations worldwide are too often not diagnosed until morbid symptoms become apparent in the late phase. Obtaining an early and accurate diagnosis that reveal a hidden lethal threat before the disease becomes complicated may dramatically reduce the severity of its impact on the patient’s life and increase the probability of survival. For example, in the case of ovarian cancer, which is the fifth most common malignancy and the fifth leading cause of cancer mortality in women in the US, the 5-year relative survival is …

Exosomes Released From Multiple Myeloma Cells Influence The Angiogenic Function Of Endothelial Cells By Regulating Microrna-29b, Qinmao Ye

Browse all Theses and Dissertations

Multiple myeloma is a hematological malignancy characterized by clonal proliferation of plasma cells generally caused by chromosomal abnormalities. It occurs in the bone marrow, which is the microenvironment of multiple myeloma. Exosomes (EXs) are 30-100 nm membrane-derived micro-vesicles containing various of bioactive molecules, such as microRNAs, to mediate the cell-cell interaction. Numerous studies reported that exosomes play a significant role in tumor microenvironment. Angiogenesis has the important implication in tumor exacerbation to supply nutrients to promote the progression of cancer cells through endothelial cells (ECs). Some studies demonstrated that microRNA-29b (miR-29b) can suppress tumor development and inhibit angiogenesis. Therefore, in …

Mitochondria-To-Nucleus Retrograde Signaling And Its Role In Cancer, Trevor Carden

All ETDs from UAB

Mitochondrial dysfunction is considered a hallmark of cancer. Mitochondria are essential, cellular organelles that participate in processes including energy production, calcium homeostasis and steroid metabolism. Mitochondria have been more recently appreciated for their role in cellular signaling, bringing about a greater understanding of their role in many diseases including cancer. Retrograde signaling is a mechanism by which the nucleus responds to mitochondrial dysfunction by modulating its own transcriptional programs to maintain metabolic and cellular processes. Many genes have already been identified as participants in or mediators of this signaling mechanism; these include cell signaling, metabolic and structural genes as well …

Transcriptome Analysis Of Root Development In Wheat Triticum Aestivum Using High Throughtput Sequencing Technologies, Ghana Challa

Electronic Theses and Dissertations

Root provides plant water, nutrients and anchorage from soil. Most our knowledge of molecular mechanisms of root development is from the dicot model plant Arabidopsis, but very few studies have done in monocot crop systems like rice, maize, and wheat. We are studying very short root (VSR) phenotype in wheat, and lack of a sequenced reference genome in wheat prompted us to sequence and assemble the root transcriptome of the reference cultivar Chinese Spring (CS). A root transcriptome was assembled from the sequenced reads generated from root tip and the mature root tissues of CS. Approximately 169 million reads were …