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

Yusuke Nakade; Yasunori Iwata; Kenichi Harada; Yasuharu Sato; Masashi Mita; Kenji Hamase; Ryuichi Konno; Mayo Hayashi; Taku Kobayashi; Yuta Yamamura; Tadashi Toyama; Atsushi Tajima; Takashi Wada

doi:10.1007/s00726-024-03426-1

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

Amino Acids. 2024 Dec 24;57(1):4. doi: 10.1007/s00726-024-03426-1.

Authors

Yusuke Nakade^{1

2}, Yasunori Iwata^{1

2}, Kenichi Harada³, Yasuharu Sato⁴, Masashi Mita⁵, Kenji Hamase⁶, Ryuichi Konno⁷, Mayo Hayashi^{1

2}, Taku Kobayashi¹, Yuta Yamamura¹, Tadashi Toyama¹, Atsushi Tajima⁸, Takashi Wada⁹

Affiliations

¹ Department of Nephrology and Rheumatology, Kanazawa University, 13-1 Takara-Machi, Kanazawa, 920-8641, Japan.
² Department of Clinical Laboratory, Kanazawa University Hospital, 13-1 Takara-Machi, Kanazawa, 920-8641, Japan.
³ Department of Human Pathology, Kanazawa University Graduate School of Medicine, 13-1 Takara-Machi, Kanazawa, 920-8641, Japan.
⁴ Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences, 2-5-1 Shikata-Chou, Kita-Ku, Okayama, 700-8558, Japan.
⁵ KAGAMI Co., Ltd., 7-18 Saitobaiohiruzu Centre 308, Ibaragi-Shi, Osaka, 567-0085, Japan.
⁶ Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
⁷ Department of Pharmaceutical Sciences, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, 324-8501, Japan.
⁸ Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, 13-1 Takara-Machi, Kanazawa, 920-8641, Japan.
⁹ Department of Nephrology and Rheumatology, Kanazawa University, 13-1 Takara-Machi, Kanazawa, 920-8641, Japan. twada@staff.kanazawa-u.ac.jp.

PMID: 39718666
DOI: 10.1007/s00726-024-03426-1

Abstract

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.

Keywords: D-amino acid; D-amino acid oxidase; D-aspartate oxidase; Diffuse large B-cell lymphoma; Serine racemase.

MeSH terms

Amino Acids / metabolism
Animals
Female
Gene Expression Regulation, Neoplastic
Humans
Lymphoma, Large B-Cell, Diffuse* / genetics
Lymphoma, Large B-Cell, Diffuse* / metabolism
Lymphoma, Large B-Cell, Diffuse* / pathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout*

Substances

Amino Acids

Abstract

MeSH terms

Substances

Grants and funding