TY - JOUR
T1 - 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
AU - Nakade, Yusuke
AU - Iwata, Yasunori
AU - Harada, Kenichi
AU - Sato, Yasuharu
AU - Mita, Masashi
AU - Hamase, Kenji
AU - Konno, Ryuichi
AU - Hayashi, Mayo
AU - Kobayashi, Taku
AU - Yamamura, Yuta
AU - Toyama, Tadashi
AU - Tajima, Atsushi
AU - Wada, Takashi
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2025/12
Y1 - 2025/12
N2 - 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−/−) 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−/− 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.
AB - 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−/−) 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−/− 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.
KW - D-amino acid
KW - D-amino acid oxidase
KW - D-aspartate oxidase
KW - Diffuse large B-cell lymphoma
KW - Serine racemase
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UR - http://www.scopus.com/inward/citedby.url?scp=85212827404&partnerID=8YFLogxK
U2 - 10.1007/s00726-024-03426-1
DO - 10.1007/s00726-024-03426-1
M3 - Article
C2 - 39718666
AN - SCOPUS:85212827404
SN - 0939-4451
VL - 57
JO - Amino Acids
JF - Amino Acids
IS - 1
M1 - 4
ER -
