Significance of signal recognition particle 9 nuclear translocation: Implications for pancreatic cancer prognosis and functionality

Sato,Hiromichi; Meng,Sikun; Sasaki,Kazuki; Kobayashi,Shogo; Kido,Kansuke; Tsuji,Yoshiko; Arao,Yasuko; Saito,Yoshiko; Iwagami,Yoshifumi; Yamada,Daisaku; Tomimaru,Yoshito; Noda,Takehiro; Takahashi,Hidenori; Motooka,Daisuke; Uchida,Shizuka; Ofusa,Ken; Satoh,Taroh; Doki,Yuichiro; Eguchi,Hidetoshi; Hara,Tomoaki; Ishii,Hideshi

doi:10.3892/ijo.2024.5662

Significance of signal recognition particle 9 nuclear translocation: Implications for pancreatic cancer prognosis and functionality

Authors:
- Hiromichi Sato
- Sikun Meng
- Kazuki Sasaki
- Shogo Kobayashi
- Kansuke Kido
- Yoshiko Tsuji
- Yasuko Arao
- Yoshiko Saito
- Yoshifumi Iwagami
- Daisaku Yamada
- Yoshito Tomimaru
- Takehiro Noda
- Hidenori Takahashi
- Daisuke Motooka
- Shizuka Uchida
- Ken Ofusa
- Taroh Satoh
- Yuichiro Doki
- Hidetoshi Eguchi
- Tomoaki Hara
- Hideshi Ishii
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Affiliations: 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, Department of Pathology, Osaka University Graduate School of Medicine, Osaka 565‑0871, Japan, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka 565‑0871, Japan, Center for RNA Medicine, Department of Clinical Medicine, Aalborg University, DK‑2450 Copenhagen, Denmark
Published online on: June 6, 2024 https://doi.org/10.3892/ijo.2024.5662
Article Number: 74
Copyright: © Sato et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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