Role of AR-Derived Circular RNA in Prostate Cancer
Abstract
The androgen receptor (AR) is a key therapeutic target in prostate cancer. Multiple AR 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 successfully initiated the study in spite of limitations and challenges posed by the pandemic. All regulatory documents were 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. In Year 2, we completed the identification of circARs in prostate cancer cell lines by probe-based RNA-seq. In Year 3, we completed some functional studies of circARs, and found that some of the circARs may affect the cell proliferation by inhibiting AR variant expression. We also optimized methodology in identifying circAR-interacting RNAs and proteins. Although we did not complete all proposed tasks in 3 years, we expect to finish and report more discoveries in the extended 4th years.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2023
- Accession Number
- AD1206354
Entities
People
- Changxue Lu
Organizations
- Johns Hopkins University