The long non-coding RNA PCAL7 promotes prostate cancer by strengthening androgen receptor signaling.

The prostate cancer (PCa) has been a global problem to men health. Notably, the androgen receptor (AR) is essential for both normal development of prostate and prostate cancer progression.

The RNA sequencing was used to identify the novel long non-coding RNA (lncRNA) termed PCAL7. The RT-qPCR was performed to quantify PCAL7 expression. Migration and proliferation assays were used to examine the function of PCAL7. Fluorescence in situ hybridization (FISH) was used to determine subcellular localization.

By RNA sequencing, the differentially expressed lncRNAs were identified (top 10 upregulated lncRNAs: PCAL7, AC083843.1, CTC-338M12.3, RP11-443B7.1, RP11-1008C21.2, RN7SL329P, RP4-773N10.4, RP11-264B17.2, KB-1507C5.2, and RP11-20B24.6; top 10 downregulated lncRNAs: RP11-77H9.2, RAB11FIP1P1, AP001625.6, CTA-217C2.1, RP11-603J24.7, RP11-315I20.1, AC092839.1, RP4-758J18.10, RP11-259O2.3, and HMGN2P17). PCAL7 was the lncRNA with the highest fold upregulation and significantly correlated with AR signaling during prostate cancer progression. The AR-regulated PCAL7 was abundantly overexpressed in prostate cancer tissues and AR-dependent cell lines. PCAL7 knockdown inhibited cell migration and proliferation. Consistently, the migration and proliferation were promoted by PCAL7 overexpression. PCAL7 depletion via antisense oligonucleotides (ASOs) markedly suppressed AR signaling and tumor growth. Mechanistically, PCAL7 interacted with Huntingtin-interacting protein 1 (HIP1) to stabilize HIP1. Therefore, PCAL7 could advance AR signaling via a novel positive feedback loop.

Our experiments support an oncogenic role for PCAL7 which promotes prostate cancer progression suggesting PCAL7 may serve as a potential therapeutic target.

Journal of clinical laboratory analysis. 2020 Nov 21 [Epub ahead of print]

Zhihui Li, Jingfei Teng, Zhuomin Jia, Guohui Zhang, Xing Ai

Department of Urology, The Seventh Medical Center of PLA General Hospital, Beijing, China.