Mechanism of activating transcription factor 4 promoting benign prostatic hyperplasia using single-cell RNA sequencing
10.12483/j.issn.1009-8291.2026.05.012
- VernacularTitle:基于单细胞RNA测序分析激活转录因子4促进良性前列腺增生的机制研究
- Author:
Junyan XU
1
;
Yuhan GUO
1
;
Jiaohuang CHEN
1
;
Xueting SUN
1
;
Zhong WANG
2
;
Yanting SHEN
2
Author Information
1. School of Gongli Hospital, University of Shanghai for Science and Technology, Shanghai 200135; Dpartment of Urology and Andrology, Gongli Hospital of Shanghai Pudong New Area, Shanghai 200135, China
2. Dpartment of Urology and Andrology, Gongli Hospital of Shanghai Pudong New Area, Shanghai 200135, China
- Publication Type:Journal Article
- Keywords:
benign prostatic hyperplasia;
single-cell RNA sequencing;
activating transcription factor 4;
epithelialmesenchymal transition
- From:
Journal of Modern Urology
2026;31(5):460-466
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of activating transcription factor 4 (ATF4) in benign prostatic hyperplasia (BPH) in order to elucidate the molecular mechanism underlying BPH progression. Methods Firstly, we analyzed the correlation between the expression of ATF4 and the volume of prostate transition zone in BPH tissues using publicly available datasets. Subsequently, we explored the potential association among ATF4, epithelial-mesenchymal transition (EMT) and BPH through single-cell RNA sequencing (scRNA-seq). Finally, we validated the findings by silencing ATF4 and treating BPH cells with ATF4 protein inhibitors, followed by reverse transcription quantitative polymerase chain reaction (RT-qPCR), CCK-8 assay, and Western blot. Results The expression of ATF4 in BPH tissues exhibited a significant positive correlation with the volume of prostate transition zone (r=0.64, P＜0.05). scRNA-seq analysis revealed that ATF4 was significantly upregulated in the prostate epithelial cells of BPH patients (P＜0.05), and its expression demonstrated a significant positive correlation with the Hallmark EMT singscore (r=0.14, P＜0.05). In vitro experiments further indicated that knockdown of ATF4 led to a significant reduction in the proliferative activity of BPH-1 cells (P＜0.05). Similarly, inhibition of ATF4 activity resulted in a marked decrease in the proliferative capacity and EMT of BPH-1 cells (P＜0.05). Conclusion ATF4 may exert a promoting effect on BPH by modulating the EMT signaling pathway;therefore, ATF4 may serve as a novel therapeutic target of BPH.
