Northwestern Medicine investigators have discovered that a novel long noncoding RNA (lncRNA), which are usually 200 nucleotides longer than typical RNAs and are widely expressed in cells, could serve as a prognostic biomarker and therapeutic target for prostate cancer, according to a recent study published in Science Advances.
Qi Cao, PhD, the Anthony J. Schaeffer, MD, Professor of Urology, and Rendong Yang, PhD, associate professor of Urology, were co-corresponding authors of the study.
Prostate cancer is the second-leading cause of cancer-related death among men in the U.S., with more than 600,000 cancer-related deaths diagnosed in 2024 alone, according to a recent report from the American Cancer Society.
Increasing studies suggest that long noncoding lncRNAs support prostate cancer tumor growth and progression, however the regulatory mechanisms of lncRNAs in prostate cancer have remained unclear.
Using advanced RNA sequencing techniques to analyze multiple prostate cancer patient tissues samples and cell lines, Cao’s team discovered that lncRNA transcript 71 (PRCAT71) was highly expressed exclusively in metastatic and primary prostate cancer tissue.
Furthermore, the investigators found that targeting PRCAT71 reduced cancerous properties of prostate cancer cells, specifically cell proliferation, colony formation and invasiveness.
They also discovered that PRCAT71 recruits the KHSRP protein to androgen receptor mRNA, stabilizing androgen receptor mRNA and increasing androgen receptor signaling. This signaling is known as a “master regulator” of prostate cancer progression.
The findings suggest that PRCAT71 may be a potential diagnostic and prognostic biomarker and therapeutic target for patients with prostate cancer. Going forward, the investigators aim to further investigate the non-canonical role of KHSRP in prostate cancer and other cancers.
“Our study demonstrates a coordinated regulation of androgen receptor 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 prostate cancer,” the authors wrote.
Yongyong Yang, PhD, a postdoctoral fellow in the Cao laboratory, was lead author of the study.
Zhe Ji, PhD, assistant professor of Pharmacology, and Edward Schaeffer, MD, PhD, chair and the Harold Binstein Professor of Urology, were co-authors of the study.
Cao, Yang, Ji and Schaeffer are members of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
This work was supported in part by grants from the Department of Defense W81XWH-21-1-0146, HT9425-23-1-0491 and W81XWH-20-1-0504; National Institutes of Health grants R01CA278832, R01CA256741, R01CA285684, R01CA259388, R35GM142441, R35GM138192, and R01HL161389 ; Canadian Institute of Health Research PJT156150, PJT178063, and PJT196012; Prostate SPORE P50CA180995 Development Research Program; and the Polsky Urologic Cancer Institute of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University at Northwestern Memorial Hospital.
