Androgen receptor–regulated lncRNA PRCAT71 promotes AR signaling through the interaction with KHSRP in prostate cancer
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.
Authors
- Qingxiang Guo (ORCID: https://orcid.org/0000-0002-3694-3428)
- Tamara L. Lotan (ORCID: https://orcid.org/0000-0002-0494-9067)
- Jiawen Lu (ORCID: https://orcid.org/0000-0002-4815-8574)
- Edward M. Schaeffer (ORCID: https://orcid.org/0000-0003-0699-1899)
- Joshua Fry (ORCID: https://orcid.org/0000-0002-2503-611X)
- Adam B. Weiner (ORCID: https://orcid.org/0000-0002-1912-042X)
- Zhe Ji (ORCID: https://orcid.org/0000-0002-1809-8099)
- Yu Wan (ORCID: https://orcid.org/0000-0003-1649-9611)
- Qi Cao (ORCID: https://orcid.org/0000-0002-5140-3681)
- Qianru Li (ORCID: https://orcid.org/0000-0002-4193-1675)
- Yanan Ren (ORCID: https://orcid.org/0000-0001-9586-3690)
- Xuesen Dong (ORCID: https://orcid.org/0000-0002-3115-3371)
- Rendong Yang (ORCID: https://orcid.org/0000-0002-9512-2240)
- Ting-You Wang (ORCID: https://orcid.org/0000-0003-4354-3198)
- Chaehyun Yum
- Yongyong Yang (ORCID: https://orcid.org/0000-0003-2297-5848)
- Qi Liu (ORCID: https://orcid.org/0000-0002-7652-4201)
- Rui Wang (ORCID: https://orcid.org/0009-0001-9020-4984)
Institutions
- Northwestern University (US)
- University of British Columbia (CA)
- Johns Hopkins University (US)
- University of California, Los Angeles (US)
- Johns Hopkins Medicine (US)
- Vancouver General Hospital (CA)
Publication Details
- Journal
- Science Advances
- Published
- 2025-04-09
- DOI
- https://doi.org/10.1126/sciadv.adk6989
- Citations
- 2
- Primary Topic
- Cancer-related molecular mechanisms research
- Type
- article
- Field-Weighted Citation Impact
- 1.87