2. Academic Validation
  3. Androgen receptor-regulated lncRNA PRCAT71 promotes AR signaling through the interaction with KHSRP in prostate cancer

Androgen receptor-regulated lncRNA PRCAT71 promotes AR signaling through the interaction with KHSRP in prostate cancer

  • Sci Adv. 2025 Apr 11;11(15):eadk6989. doi: 10.1126/sciadv.adk6989.
Yongyong Yang 1,  Ting-You Wang 1,  Qianru Li 2,  Jiawen Lu 1,  Yanan Ren 1,  Adam B Weiner 3,  Joshua Fry 1,  Qi Liu 1,  Chaehyun Yum 1,  Rui Wang 1,  Qingxiang Guo 1,  Yu Wan 4,  Zhe Ji 2 4,  Xuesen Dong 5 6,  Tamara L Lotan 7,  Edward M Schaeffer 1 8,  Rendong Yang 1 8,  Qi Cao 1 8
Affiliations

Affiliations

  • 1 Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
  • 2 Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
  • 3 Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • 4 Department of Biomedical Engineering, Northwestern University McCormick School of Engineering, Evanston, IL 60628, USA.
  • 5 Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC V6H 3Z6, Canada.
  • 6 Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.
  • 7 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • 8 Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
PMID: 40203114 DOI: 10.1126/sciadv.adk6989
Abstract

Mounting evidence indicates that long noncoding RNAs (lncRNAs) play vital roles in tumorigenesis and progression of cancers. However, the functions and regulatory mechanisms of lncRNAs in prostate Cancer (PCa) are still largely unknown. In this study, we found an lncRNA, PCa-associated transcript 71 (PRCAT71), highly expressed in metastatic and primary PCa compared to benign prostate tissues. Silencing PRCAT71 inhibited cancerous properties of PCa cells and Androgen Receptor (AR) signaling. Mechanistically, PRCAT71 acts as a scaffold to recruit K homology (KH)-type splicing regulatory protein (KHSRP) to AR messenger RNA (mRNA) and stabilize AR mRNA, leading to activated AR signaling. KHSRP plays a critical role in PCa progression. PRCAT71 is transcriptionally regulated by AR-driven enhancers, forming a positive regulatory loop between AR and PRCAT71 in PCa. Our study demonstrates a coordinated regulation of AR mRNA by lncRNA PRCAT71 and RNA binding protein KHSRP and provides insight that the PRCAT71-KHSRP-AR axis is a promising therapeutic target for treating PCa.

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