UBC Theses and Dissertations
Circular RNA of the androgen receptor gene in prostate cancer Shi, Yao
The androgen receptor (AR) gene is important for prostate cancer development and tumor progression. The protein encoded by the AR gene is the mainstay therapeutic target for metastatic prostate cancers. Alterations in mRNAs transcribed by the AR gene are also biomarkers of therapy-resistant prostate cancers. These alterations are induced by alternative RNA splicing of the AR gene, AR gene amplification, or gain-of-function mutations of the AR gene. Non-coding RNAs derived from the AR gene may also serve as biomarkers of disease progression of prostate cancers. Circular RNA (circRNA) is one subtype of non-coding RNAs that have been demonstrated to be abundantly expressed in human cells and is highly resistant to exonuclease digestion. It is generated by RNA splicing machinery through back-splicing processes. In this thesis, I have demonstrated that there are two circRNAs derived from the AR gene, namely CirAR2 and CirAR3. These circRNAs are widely expressed in AR-positive prostate cancer cells. The expressions of these circRNAs are elevated by androgen deprivation and anti-androgens. I have constructed expression vectors encoding CirAR3 and showed that CirAR3 does not alter AR protein expression as well as ligand-dependent AR transcriptional activities. However, I demonstrated that CirAR3 is resistant to Ribonuclease R digestion, and has a significantly longer half-life than linear AR mRNAs. CirAR3 can be detected by real-time PCR in less than 10 AR-positive 22Rv1 prostate cancer cells. In summary, these studies suggest that circRNAs derived from the AR gene may be potential biomarkers of prostate cancers.
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