Jiang Xin, Li Ji, Zhang Jiali, Zhao Yulei, He Guoqin, Yao Xiaohui
Baoying People's Hospital, 1 Xincheng Road, Baoying, Yangzhou, 225800, Jiangsu Province, China.
Xiaoguanzhuang Town Health Center, Yangzhou, Jiangsu Province, China.
Sci Rep. 2025 Jul 4;15(1):23847. doi: 10.1038/s41598-025-04629-6.
Aberrant activation/overexpression of RNF126 is implicated as a driving event in tumor progression. However, although some functions of RNF126 in prostate cancer (PCa) cell lines has been reported, more biological functions and in-depth mechanisms should be further clarified in PCa.
Here, we provide evidence that RNF126 expression is elevated in human PCa tissues and cell lines, which is associated with tumor grades and prognosis. Cell proliferation was measured by the CCK8 and colony-formation assays. Cell migration was performed by Transwell and wound-healing assays. RNF126 target proteins were investigated via proteomic, co-immunoprecipitation and western blot methods. Additionally, we knock-downed MBNL1 expression to perform rescue experiments. In vivo, xenograft mice assay was used to verify the effect of RNF126 on the growth of PCa cell.
Here, we showed that RNF126 was highly expressed in PCa and its higher expression was associated with worse patients' prognosis. Expression modulation of RNF126 affects PCa cells proliferation, migration, EMT and docetaxel (DTX) resistance in vitro or in vivo. Additionally, RNF126 involves in the regulation of PI3K/AKT, MEK/ERK and EMT pathways. Mechanistically, immunoprecipitation (IP) and coimmunoprecipitation (co-IP) assays indicated that RNF126 could bind to MBNL1 directly. Our data also suggested that MBNL1 was a critical downstream event in RNF126-mediated tumorigenesis and chemo-resistance and played a crucial role in driving the PI3K/AKT, MEK/ERK and EMT pathways.
Taken together, our findings reveal a novel biological and molecular functions of RNF126 and may provide a new treatment option for PCa patients.
RNF126的异常激活/过表达被认为是肿瘤进展的驱动事件。然而，尽管已经报道了RNF126在前列腺癌细胞系中的一些功能，但在前列腺癌中更多的生物学功能和深入机制仍有待进一步阐明。
在此，我们提供证据表明RNF126在人前列腺癌组织和细胞系中表达升高，这与肿瘤分级和预后相关。通过CCK8和集落形成试验检测细胞增殖。通过Transwell和伤口愈合试验检测细胞迁移。通过蛋白质组学、免疫共沉淀和蛋白质印迹方法研究RNF126的靶蛋白。此外，我们敲低MBNL1表达以进行挽救实验。在体内，采用异种移植小鼠试验验证RNF126对前列腺癌细胞生长的影响。
在此，我们表明RNF126在前列腺癌中高表达，其较高表达与患者预后较差相关。RNF126的表达调节在体外或体内影响前列腺癌细胞的增殖、迁移、上皮-间质转化（EMT）和多西他赛（DTX）耐药性。此外，RNF126参与PI3K/AKT、MEK/ERK和EMT信号通路的调节。机制上，免疫沉淀（IP）和免疫共沉淀（co-IP）试验表明RNF126可直接与MBNL1结合。我们的数据还表明，MBNL1是RNF126介导的肿瘤发生和化疗耐药中的关键下游事件，在驱动PI3K/AKT、MEK/ERK和EMT信号通路中起关键作用。
综上所述，我们的研究结果揭示了RNF126新的生物学和分子功能，并可能为前列腺癌患者提供新的治疗选择。
