Date of Award

5-2024

Document Type

Campus Access Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Jill Macoska

Second Advisor

Shailjia Panthania

Third Advisor

Kourosh Zarringhalam

Abstract

Autopsy examinations revealed that benign prostate hyperplasia (BPH) histologically affects 80-90% of men in their 70s and older. Due to the prostate's unique position surrounding the urethra, BPH contributes to lower urinary tract dysfunction (LUTD). LUTD is characterized by painful urination and can lead to acute urinary retention, which significantly impacts the quality of life of patients. Our lab previously uncovered prostate fibrosis as an unexplored pathobiology associated with LUTD. A key attribute of fibrosis is the excessive production of extracellular matrix (ECM), triggered by inflammatory cytokines such as interleukin-4 (IL-4) and interleukin-13 (IL-13). In contrast to conventional approaches focusing on signal transduction-mediated regulation of ECM production, our novel strategy centers on understanding how regulatory RNAs control translation of ECM proteins. Regulatory RNAs include microRNA (miRNA) that bind to the 3' UTR of target mRNA to inhibit translation. Also, circular RNA (circRNA) that acts as a miRNA sponge, creating a double-negative effect to alleviate translation inhibition. These investigations aim to unveil how regulatory RNAs could be utilized by profibrotic cytokines to increase ECM protein production, contributing to fibrosis in the lower urinary tract. Through microarray analysis and RNA sequencing, we have determined differentially expressed circRNAs and miRNAs. The expression levels of identified miRNA and circRNA were validated through Quantitative Reverse Transcriptase Polymerase Chain Reaction (RT-qPCR). Leveraging our knowledge of ECM protein transcripts, circRNAs, miRNAs of interest and their potential complementary binding, a preliminary competing endogenous RNA network was established. From the ceRNA network, we identified multiple circRNAs and miRNAs of interest for future explorational studies. Future research will concentrate on further validating the roles of these RNAs and exploring their potential as therapeutic targets.

Comments

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