AI Article Synopsis

  • Signal recognition particles (SRPs), particularly SRP9, play a crucial role in cellular protein transport, and high SRP9 expression is associated with poorer survival in tumor patients, yet its specific role in pancreatic cancer prognosis has not been well-explored.
  • The study found that in some pancreatic cancer cases, SRP9 was predominantly located in the nucleus, and patients with over 50% of SRP9 translocation to the nucleus experienced significantly better recurrence-free survival compared to those with less translocation.
  • Further experiments indicated that factors like amino acid deficiency influenced SRP9 localization, and multiple splicing variants of SRP9 displayed nuclear translocation, highlighting the importance of its N-terminal regions in relation to cancer signaling

Article 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 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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11173368PMC
http://dx.doi.org/10.3892/ijo.2024.5662DOI Listing

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