Cheng Huan, Chen Zeyu, Wang Yong, Ji Chengjian, Wang Junqi, Song Ninghong
Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Department of Urology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221004, China.
Cell Biochem Biophys. 2025 Mar;83(1):1237-1248. doi: 10.1007/s12013-024-01558-5. Epub 2024 Oct 3.
Prostate cancer (PC) is the most frequently occurring cancer in men, characterized by the abnormal proliferation of cells within the prostate gland. This study explores the role of RNA binding motif protein 15B (RBM15B) in PC. RBM15B expression levels in PC patients were predicted using the Starbase database. The expression of RBM15B and proliferating cell nuclear antigen (PCNA) expression in PC cells was detected. Following RBM15B knockdown, cell proliferation assays were conducted. N6-methyladenosine (m6A) levels in PC cells were quantified, and RNA immunoprecipitation was performed to analyze the binding of m6A and YTH N-methyladenosine RNA binding protein 1 (YTHDF1) on PCNA mRNA. The stability of PCNA mRNA was assessed after treatment with actinomycin D. An in vivo nude mouse xenograft model was created to validate the role of RBM15B. The findings revealed the upregulation of RBM15B in PC. RBM15B knockdown resulted in decreased proliferation, colony formation, and EdU-positive cells. Mechanical analysis showed that RBM15B facilitated m6A modification of PCNA mRNA, leading to increasing m6A methylation. YTHDF1 bound to these m6A sites on PCNA mRNA, thus stabilizing it. Furthermore, PCNA overexpression mitigated the effects of RBM15B knockdown on PC cell proliferation. In conclusion, RBM15B promotes PC cell proliferation by enhancing the stability of PCNA mRNA through YTHDF1-mediated m6A modification.
前列腺癌（PC）是男性中最常见的癌症，其特征是前列腺腺体内细胞异常增殖。本研究探讨了RNA结合基序蛋白15B（RBM15B）在前列腺癌中的作用。使用Starbase数据库预测前列腺癌患者中RBM15B的表达水平。检测前列腺癌细胞中RBM15B的表达和增殖细胞核抗原（PCNA）的表达。在敲低RBM15B后，进行细胞增殖试验。对前列腺癌细胞中的N6-甲基腺苷（m6A）水平进行定量，并进行RNA免疫沉淀以分析m6A和YTH N-甲基腺苷RNA结合蛋白1（YTHDF1）在PCNA mRNA上的结合。在用放线菌素D处理后评估PCNA mRNA的稳定性。建立体内裸鼠异种移植模型以验证RBM15B的作用。研究结果显示前列腺癌中RBM15B上调。敲低RBM15B导致增殖、集落形成和EdU阳性细胞减少。机制分析表明，RBM15B促进PCNA mRNA的m6A修饰，导致m6A甲基化增加。YTHDF1与PCNA mRNA上的这些m6A位点结合，从而使其稳定。此外，PCNA过表达减轻了RBM15B敲低对前列腺癌细胞增殖的影响。总之，RBM15B通过YTHDF1介导的m6A修饰增强PCNA mRNA的稳定性，从而促进前列腺癌细胞增殖。
