Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Osaka 565‑0871, Japan.
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565‑0871, Japan.
Int J Oncol. 2024 Jul;65(1). doi: 10.3892/ijo.2024.5662. Epub 2024 Jun 7.
Signal recognition particles (SRPs) are essential for regulating intracellular protein transport and secretion. Patients with tumors with high SRP9 expression tend to have a poorer overall survival. However, to the best of our knowledge, no reports have described the relationship between SRP9 localization and prognosis in pancreatic cancer. Thus, the present study aimed to investigate this relationship. Immunohistochemical staining for SRP9 using excised specimens from pancreatic cancer surgery cases without preoperative chemotherapy or radiotherapy showed that SRP9 was preferentially expressed in the nucleus of the cancerous regions in some cases, which was hardly detected in other cases, indicating that SRP9 was transported to the nucleus in the former cases. To compare the prognosis of patients with SRP9 nuclear translocation, patients were divided into two groups: Those with a nuclear translocation rate of >50% and those with a nuclear translocation rate of ≤50%. The nuclear translocation rate of >50% group had a significantly better recurrence‑free survival than the nuclear translocation rate of ≤50% group (P=0.037). Subsequent experiments were conducted; notably, the nuclear translocation rate of SRP9 was reduced under amino acid‑deficient conditions, suggesting that multiple factors are involved in this phenomenon. To further study the function of SRP9 nuclear translocation, experiments were performed by introducing SRP9 splicing variants (v1 and v2) and their deletion mutants lacking C‑terminal regions into MiaPaCa pancreatic cancer cells. The results demonstrated that both splicing variants showed nuclear translocation regardless of the C‑terminal deletions, suggesting the role of the N‑terminal regions. Given that SRP9 is an RNA‑binding protein, the study of RNA immunoprecipitation revealed that signaling pathways involved in cancer progression and protein translation were downregulated in nuclear‑translocated v1 and v2. Undoubtedly, further studies of the nuclear translocation of SRP9 will open an avenue to optimize the precise evaluation and therapeutic control of pancreatic cancer.
信号识别颗粒 (SRPs) 对于调节细胞内蛋白质运输和分泌至关重要。具有高 SRP9 表达的肿瘤患者的总生存率往往较差。然而,据我们所知,尚无报道描述 SRP9 定位与胰腺癌之间的关系。因此,本研究旨在探讨这种关系。使用未经术前化疗或放疗的胰腺癌手术标本进行的 SRP9 免疫组织化学染色显示,在某些情况下,SRP9 在癌区的细胞核中优先表达,而在其他情况下则几乎检测不到,这表明 SRP9 在前者中被转运到细胞核。为了比较具有 SRP9 核易位的患者的预后,将患者分为核易位率>50%和核易位率≤50%两组。核易位率>50%组的无复发生存率明显优于核易位率≤50%组(P=0.037)。随后进行了实验;值得注意的是,在氨基酸缺乏条件下,SRP9 的核易位率降低,表明这一现象涉及多种因素。为了进一步研究 SRP9 核易位的功能,将 SRP9 剪接变异体(v1 和 v2)及其缺失突变体(缺乏 C 末端区域)引入 MiaPaCa 胰腺癌细胞中进行实验。结果表明,两种剪接变异体均显示核易位,与 C 末端缺失无关,表明 N 末端区域的作用。鉴于 SRP9 是一种 RNA 结合蛋白,RNA 免疫沉淀研究表明,与癌症进展和蛋白质翻译相关的信号通路在核易位的 v1 和 v2 中被下调。毫无疑问,对 SRP9 核易位的进一步研究将为优化胰腺癌的精确评估和治疗控制开辟一条途径。