Title

A Study of the Relationship Between the Long Noncoding RNA PRNCR1, PCGEM1, and Androgen Receptor Transcriptional Activity

Date of Award

8-2017

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Dianzheng Zhang, PhD

Second Advisor

Heather Montie, PhD

Third Advisor

Cathy Hatcher, PhD

Abstract

Androgen receptor (AR) plays important roles in prostate cancer initiation and progression. In addition to androgens, various factors affect AR transcriptional activity. However, the roles of long noncoding RNAs in AR activation are not well-defined. In this study, we focused our attention on the relationship between two long noncoding RNAs, PRNCR1 and PCGEM1, and AR transcriptional activity. Both resveratrol (RSV) and pterostilbene (PTS) can inhibit AR activity. Experiments were designed to determine if the inhibitory effects of RSV and PTS are dependent on these lncRNAs. Furthermore, it was found that when LNCaP cells are treated with R1881, a synthesized androgen, the levels of PRNCR1 and PCGEM1 are increased and decreased, respectively. Results from AR overexpression and AR knockdown suggest that AR is involved androgenmediated lncRNA regulation. On the other hand, knockdown of PRNCR1 and PCGEM1 individually has no appreciable effect on AR activity, but a simultaneous knockdown of both lncRNAs has significant effect on AR activity. In addition, both PTS and RSV are capable of counteracting R1881 effect on PRNCR1 and PCGEM1; although PTS is more potent in this regard. These results together suggest that both PRNCR1 and PCGEM1 are AR regulated genes and both of them are involved in the regulation of AR transactivation.

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