Hou Yue, Lu Haowen, Chen Saisai, Mao Likai, Huang Xuan, Xu Feng, Shu Chuanjun
Military Medical Innovation Center, Fourth Military Medical University, Xi'an, China.
Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, Jiangsu, China.
Front Immunol. 2025 May 30;16:1576835. doi: 10.3389/fimmu.2025.1576835. eCollection 2025.
Prostate cancer (PCa) remains the fifth leading cause of male cancer mortality, necessitating novel biomarkers and therapeutic targets.
Through BG4 ChIP-seq profiling in PCa cells, we identified promoter G-quadruplex (G4) structures in prognosis-associated genes, with GPR137C exhibiting a functional G4 in its promoter.
This G4 structure facilitates promoter hypomethylation to activate GPR137C transcription. Moreover, GPR137C promotes tumor microenvironment remodeling by enhancing immune cell infiltration, thereby driving PCa progression.
This study establishes promoter G4s as epigenetic regulators in PCa while proposing GPR137C as both a prognostic biomarker and a therapeutic nexus for GPCR-targeted drug development.
前列腺癌(PCa)仍是男性癌症死亡的第五大主要原因,因此需要新的生物标志物和治疗靶点。
通过对前列腺癌细胞进行BG4染色质免疫沉淀测序(ChIP-seq)分析,我们在预后相关基因中鉴定出启动子G-四链体(G4)结构,其中GPR137C在其启动子中表现出功能性G4。
这种G4结构促进启动子低甲基化以激活GPR137C转录。此外,GPR137C通过增强免疫细胞浸润促进肿瘤微环境重塑,从而推动前列腺癌进展。
本研究将启动子G4确立为前列腺癌中的表观遗传调节因子,同时提出GPR137C作为预后生物标志物以及用于GPCR靶向药物开发的治疗关联靶点。