Publication Date
2019
Document Type
Dissertation
Committee Members
Scott Baird (Advisor), Paula Bubulya (Committee Member), Michael Raymer (Committee Member), Sangeeta Agrawal (Committee Member), Nancy Kelley-Loughnane (Committee Member)
Degree Name
Doctor of Philosophy (PhD)
Abstract
Barrett’s Esophagus (BE) is characterized by the appearance of an intestinal-like epithelium in the distal esophagus. The molecular mechanisms behind BE development are unknown. BE is often preceded by Gastroesophageal Reflux Disease (GERD) and predisposes patients to esophageal adenocarcinoma (EAC). Due to the high mortality rate associated with EAC, BE patients are continuously monitored through upper endoscopy with biopsy for progression to low grade dysplasia (LGD), high grade dysplasia, and EAC. This monitoring technique poses numerous risks, so alternative surveillance and diagnostic techniques for BE pathogenesis are continually studied. microRNA biomarkers in BE pathogenesis may provide alternative means of diagnosis as well as a greater understanding of BE and its progression to EAC. Here, small RNA-sequencing of serum and tissue from GERD, BE, LGD, and EAC patients revealed three candidate tissue microRNAs differentially expressed in BE compared to GERD patients. Differential expression of the three candidate microRNAs was validated in a second cohort of BE and GERD patient tissues by quantitative PCR. Gene target analysis revealed two candidate microRNAs are homeobox (HOX) microRNAs, which directly target central and posterior HOX genes. HOX genes are transcription factors which regulate gene expression along the anterior/posterior axis. BE resembles a homeotic transformation, which could be due to aberrant expression of posterior HOX genes in the esophagus, an anterior organ. The third candidate microRNA targets a component of Polycomb Repressive Complex 1, a transcriptional repressor of HOX genes. Thus, the three candidate microRNAs may modulate posterior HOX gene expression associated with BE development.
Page Count
148
Department or Program
Biomedical Sciences
Year Degree Awarded
2019
Copyright
Copyright 2019, some rights reserved. My ETD may be copied and distributed only for non-commercial purposes and may not be modified. All use must give me credit as the original author.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
