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.

PRCAT71 is a PCa-specific lncRNA

(A) Heatmap of differentially expressed lncRNAs annotated by MiTranscriptome across normal prostate and PCa tissues in TCGA prostate RNA-seq data from MiTranscriptome. Reported PCa lncRNAs are listed. (B) Expression level of PRCAT71 across different cancer types in the expression data from MiTranscriptome. Inset, PRCAT71 is higher expressed in PCa tissues compared to the paired normal prostate (n = 52, P < 0.0001, Student’s t test) in TCGA prostate RNA-seq data. FPKM, fragments per kilobase of transcript per million mapped reads. (C) Efficiency of stable knockdown of PRCAT71 by two shRNAs in C4-2 cells was verified by qRT-PCR. (D) The effect of knocking down PRCAT71 on C4-2 cell proliferation was determined by CellTiter-Glo 2.0 cell viability assay. (E) The effect of knocking down PRCAT71 on C4-2 cell cycle. (F) The effect of knocking down PRCAT71 on C4-2 cell apoptosis. (G) The effect of knocking down PRCAT71 on C4-2 cell colony formation. (H) The effect of knocking down PRCAT71 on C4-2 cell migration. Data in (C) to (H) are shown as means ± SEM, n = 3. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, Student’s t test.

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.

Source – Northwestern Medicine