PDF(Pubmed)
Abstract：
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 in vitro 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, in vitro 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.
摘要：
信号识别颗粒（SRP）对于调节细胞内蛋白质的运输和分泌至关重要。具有高SRP9表达的肿瘤患者倾向于具有较差的总体存活率。然而,据我们所知,尚无报道描述SRP9定位与胰腺癌预后之间的关系。因此，本研究旨在探讨这种关系。使用未术前化疗或放疗的胰腺癌手术病例的切除标本对SRP9进行免疫组织化学染色显示，在某些情况下，SRP9优先在癌区的细胞核中表达，在其他情况下几乎没有发现，表明在前者中SRP9被转运到细胞核。比较SRP9核易位患者的预后,患者分为两组:核移位率>50%的患者和核移位率≤50%的患者.>50%组核转位率显著优于≤50%组核转位率(P=0.037)。随后进行了体外实验；特别是，在氨基酸缺乏的条件下，SRP9的核易位率降低，这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，通过将SRP9剪接变体（v1和v2）及其缺失C末端区域的缺失突变体引入MiaPaCa胰腺癌细胞进行体外实验。结果表明，无论C端缺失如何，两个剪接变体都显示出核易位，建议N端区域的作用。鉴于SRP9是一种RNA结合蛋白，RNA免疫沉淀的研究表明，参与癌症进展和蛋白质翻译的信号通路在核转位的v1和v2中下调。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.
