Francis, Cynthia Marian Rebecca
(2019)
Investigating circulating MicroRNA expression in systemic lupus erythematosus.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disorder, which is caused by the loss of immune tolerance, resulting in the production of autoantibodies directed against several self-antigens in the body. MicroRNAs (miRNAs) are a class of small noncoding RNA molecules that are involved in regulation of post-transcriptional gene expression and play an important role in immune regulation and autoimmunity. Circulating miRNAs have recently emerged as potential biomarker candidates for various human conditions, including autoimmune diseases. The primary objective of this study was to utilize a comprehensive plasma miRNA profiling data from an SLE case-control discovery sample to identify a candidate set of highly SLE-relevant circulating miRNAs to be further evaluated in large follow-up studies. The miRNA profiling data were produced using the miScript Human miRBase Profiler HC series of PCR arrays that contained 2402 human miRNA qPCR assays. A total of 280 plasma miRNAs showed >2-fold expression difference between SLE cases and controls, of which 66 showed >25 fold down-regulation in SLE patients as compared to SLE-free controls. Of those 280 plasma miRNAs, 178 exhibited significant down-regulation (P<5x10-2) in SLE including some previously reported SLE-associated circulating miRNAs as well as a number of newly identified ones. In silico assessment of the biological functions/pathways regulated by 66 highly SLE-relevant circulating miRNAs using DIANA-mirPath v3.0 (both KEGG and GO/biological process analyses) has revealed a large number of targeted pathways/categories including those involved in immune regulation/response, apoptotic processes, and epigenetic regulation, which are already known to be involved in SLE pathogenesis, as well as some potentially new biological pathways/processes. In summary, this discovery study has identified several highly SLE-relevant (previously reported + novel) plasma miRNAs that appear to contribute to SLE-associated circulating miRNA signature and warrant further confirmation/validation as potential biomarkers in large follow-up samples and independent studies. Development of clinically useful biomarkers is essential for better management of this chronic systemic disease that affects relatively young adults and poses an important public health issue.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Francis, Cynthia Marian Rebecca | cyf4@pitt.edu | cyf4 | |
|
| ETD Committee: |
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| Date: |
21 June 2019 |
| Date Type: |
Publication |
| Defense Date: |
12 April 2019 |
| Approval Date: |
21 June 2019 |
| Submission Date: |
4 April 2019 |
| Access Restriction: |
5 year -- Restrict access to University of Pittsburgh for a period of 5 years. |
| Number of Pages: |
51 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Human Genetics |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
No |
| Uncontrolled Keywords: |
Lupus, SLE, miRNA, plasma, circulating |
| Date Deposited: |
21 Jun 2019 21:57 |
| Last Modified: |
24 Jun 2019 13:22 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/36348 |
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