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:https://doi.org/10.3892/ijo.2024.5662

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

Sato, Hiromichi; Meng, Sikun; Sasaki, Kazuki et al.

International Journal of Oncology, 2024, 65(1), 74

Number of Access:2,515（2025-07-19 21:03 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/98265

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Title	Significance of signal recognition particle 9 nuclear translocation: Implications for pancreatic cancer prognosis and functionality
Creator	CreatorName Sato, Hiromichi
	NRID 1000050977204 1000050977204 researchmap permalink sikunmeng sikunmeng CreatorName Meng, Sikun
	NRID 1000020745442 1000020745442 researchmap permalink Kazuki_Sasaki Kazuki_Sasaki Scopus Author ID 56087041900 56087041900 CreatorName Sasaki, Kazuki
	NRID 1000030452436 1000030452436 researchmap permalink 30452436 30452436 Scopus Author ID 7405376089 7405376089 ORCID 0000-0002-8828-1067 0000-0002-8828-1067 CreatorName Kobayashi, Shogo
	researchmap permalink kansukekido kansukekido CreatorName Kido, Kansuke
	CreatorName Tsuji, Yoshiko
	NRID 1000070962736 1000070962736 CreatorName Arao, Yasuko
	CreatorName Saito, Yoshiko
	NRID 1000060597441 1000060597441 researchmap permalink yiwagami yiwagami Scopus Author ID 35074034100 35074034100 CreatorName Iwagami, Yoshifumi
	NRID 1000060571396 1000060571396 ORCID 0000-0002-6702-3800 0000-0002-6702-3800 researchmap permalink dyamada79222 dyamada79222 Scopus Author ID 37008067700 37008067700 CreatorName Yamada, Daisaku
	NRID 1000070528570 1000070528570 researchmap permalink yoshitotomimaru yoshitotomimaru Scopus Author ID 10240341100 10240341100 CreatorName Tomimaru, Yoshito
	NRID 1000050528594 1000050528594 researchmap permalink t-noda t-noda Scopus Author ID 12764559600 12764559600 ORCID 0000-0002-6768-5783 0000-0002-6768-5783 CreatorName Noda, Takehiro
	NRID 1000090601120 1000090601120 ORCID 0000-0003-4801-3540 0000-0003-4801-3540 researchmap permalink hdnr_tkhs hdnr_tkhs Scopus Author ID 7405468781 7405468781 CreatorName Takahashi, Hidenori
	NRID 1000010636830 1000010636830 researchmap permalink daisukem daisukem Scopus Author ID 35315737900 35315737900 CreatorName Motooka, Daisuke
	CreatorName Uchida, Shizuka
	CreatorName Ofusa, Ken
	NRID 1000040368303 1000040368303 ORCID 0000-0002-4615-2638 0000-0002-4615-2638 researchmap permalink TarohSatoh TarohSatoh Scopus Author ID 12040860900 12040860900 CreatorName Satoh, Taroh
	NRID 1000020291445 1000020291445 researchmap permalink ydoki3251 ydoki3251 Scopus Author ID 7006390687 7006390687 CreatorName Doki, Yuichiro
	NRID 1000090542118 1000090542118 researchmap permalink abcdabcdabcd abcdabcdabcd Scopus Author ID 7101627772 7101627772 CreatorName Eguchi, Hidetoshi
	NRID 1000030779161 1000030779161 researchmap permalink registered20221012 registered20221012 CreatorName Hara, Tomoaki
	NRID 1000010280736 1000010280736 researchmap permalink read0103186 read0103186 Scopus Author ID 7402978600 7402978600 CreatorName Ishii, Hideshi
Subject	essential amino acids
	nuclear translocation
	pancreatic cancer
	signal recognition particle 9
	splicing variants
Description	Sato H., Meng S., Sasaki K., et al. Significance of signal recognition particle 9 nuclear translocation: Implications for pancreatic cancer prognosis and functionality. International Journal of Oncology 65, 74 (2024); https://doi.org/10.3892/ijo.2024.5662.
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.
Publisher	Spandidos Publications
Source Title	International Journal of Oncology
Volume (Issue)	65(1)
Page	74
Date of Issued	2024-07-01
Language	English
Handle URL	https://hdl.handle.net/11094/98265
PISSN	10196439
eISSN	17912423
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.3892/ijo.2024.5662
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	International Journal of Oncology. 2024, 65(1), p. 74
DC.title	Significance of signal recognition particle 9 nuclear translocation: Implications for pancreatic cancer prognosis and functionality
DC.creator	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
DC.publisher	Spandidos Publications
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-07-01
DC.identifier	https://doi.org/10.3892/ijo.2024.5662
DC.subject	essential amino acids
	nuclear translocation
	pancreatic cancer
	signal recognition particle 9
	splicing variants
DC.description	Sato H., Meng S., Sasaki K., et al. Significance of signal recognition particle 9 nuclear translocation: Implications for pancreatic cancer prognosis and functionality. International Journal of Oncology 65, 74 (2024); https://doi.org/10.3892/ijo.2024.5662.
DCTERMS.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.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	98265
citation_title	Significance of signal recognition particle 9 nuclear translocation: Implications for pancreatic cancer prognosis and functionality
citation_author	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
citation_publisher	Spandidos Publications
citation_language	English
citation_date	2024-07-01
citation_journal_title	International Journal of Oncology
citation_volume	65
citation_issue	1
citation_firstpage	74
citation_doi	https://doi.org/10.3892/ijo.2024.5662
citation_public_url	https://hdl.handle.net/11094/98265

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

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