Effect of D-amino acid metabolic enzyme deficiency on cancer development—diffuse large B-cell lymphoma onset and gene expression analyses in DASPO-knockout mice
The relationship between D-AA metabolic enzymes and cancer development remains unclear. We aimed to investigate this relationship using mice deficient in D-AA-related metabolic enzymes. We examined mice lacking these enzymes for approximately 900 days and the effects of altered D-AA metabolism on cancer development based on lifespan, pathological findings, and gene expression. The lifespan of female DASPO -knockout (DASPO<sup>-/-</sup>) mice was shorter than that of the other group mice; furthermore, these mice showed tumor-like masses in the liver, spleen, and small intestine. A pathological diagnosis of diffuse large B-cell lymphoma (DLBCL) was made. RNA sequencing of the liver samples showed specific alterations in the expression of 71 genes in DASPO<sup>-/-</sup> mice compared with that in wild-type B6 mice; RGS 1, MTSS1, and SMARCD 1 were identified as DLBCL-related genes. Patients with DLBCL exhibiting low DASPO expression demonstrated a shorter survival period than those showing high expression. However, the role of DASPO in DLBCL development is unclear. Therefore, future research should focus on B cells. DASPO may serve as novel biomarkers and therapeutic targets in cancer.
Authors
- Yusuke Nakade (ORCID: https://orcid.org/0000-0002-0094-359X)
- Masashi Mita
- Kenichi Harada (ORCID: https://orcid.org/0000-0002-6451-0638)
- Yasunori Iwata
- Atsushi Tajima (ORCID: https://orcid.org/0000-0001-6808-5491)
- Masao Hayashi (ORCID: https://orcid.org/0000-0002-9321-7406)
- Taku Kobayashi (ORCID: https://orcid.org/0000-0002-2073-4234)
- Takashi Wada
- Yasuharu Sato (ORCID: https://orcid.org/0000-0001-5234-6861)
- Yuta Yamamura (ORCID: https://orcid.org/0000-0003-3713-0733)
- Kenji Hamase (ORCID: https://orcid.org/0000-0001-6140-4787)
- Tadashi Toyama (ORCID: https://orcid.org/0000-0003-0162-6286)
- Ryuichi Konno
Institutions
- Kanazawa University (JP)
- Kyushu University (JP)
- Okayama University (JP)
- Kanazawa University Hospital (JP)
- Kagami Crystal (Japan) (JP)
- International University of Health and Welfare (JP)
Publication Details
- Journal
- Amino Acids
- Published
- 2024-12-24
- DOI
- https://doi.org/10.1007/s00726-024-03426-1
- Citations
- 1
- Primary Topic
- Amino Acid Enzymes and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 0.29
Funders
- Japan Agency for Medical Research and Development
- Kanazawa University