Role of AR-Derived Circular RNA in Prostate Cancer
[Technical Report, Annual Report]
JOHNS HOPKINS UNIV BALTIMORE MD
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The androgen receptor is a key therapeutic target in prostate cancer. Multiple androgen receptor alterations are known to affect prostate cancer progression and treatment efficacy. In this proposal, we will focus on a novel form of non-coding circular RNA originated from the androgen receptor gene. We will test the hypothesis that AR-derived, non-coding circular RNAs circARs can act as competitive endogenous RNAs through sponging micro RNA miRNA, or RNA-binding proteins to regulate prostate cancer progression. To this end, we proposed three Specific Aims. Aim 1 will identify and validate circARs in castration resistance prostate cancer CRPC. Aim 2 will define the functional roles of circARs in CRPC. Aim 3 will determine the regulatory factors involved in circAR generation. During Year 1 of the funding period, we have successfully initiated the study in spite of limitations and challenges posed by the pandemic. All regulatory documents are now in compliance with the latest regulations. We established and validated the methodology to enrich AR transcripts for identifying circular ARs by RNA-seq in prostate cancer cell lines. Although we have not generated definitive results, with expansion of the established method to prostate cancer patient tissues, we expect to report main in the next two years of the project period.
- Medicine and Medical Research