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

IF 3 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Amino Acids Pub Date : 2024-12-24 DOI:10.1007/s00726-024-03426-1

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

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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.

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d -氨基酸代谢酶缺乏对daspo基因敲除小鼠肿瘤发展-弥漫性大b细胞淋巴瘤发病及基因表达的影响

D-AA代谢酶与癌症发展之间的关系尚不清楚。我们的目的是用缺乏d - aa相关代谢酶的小鼠来研究这种关系。我们对缺乏这些酶的小鼠进行了大约900天的研究，并根据寿命、病理结果和基因表达对D-AA代谢改变对癌症发展的影响进行了研究。DASPO基因敲除雌性（DASPO−/−）小鼠寿命短于其他组小鼠；此外，这些小鼠的肝脏、脾脏和小肠均出现肿瘤样肿块。病理诊断为弥漫性大b细胞淋巴瘤（DLBCL）。肝脏样本的RNA测序显示，与野生型B6小鼠相比，DASPO−/−小鼠中71个基因的表达发生了特异性变化；RGS 1、MTSS1和SMARCD 1被鉴定为dlbcl相关基因。DASPO低表达的DLBCL患者比DASPO高表达的患者生存期短。然而，DASPO在DLBCL发展中的作用尚不清楚。因此，今后的研究重点应放在B细胞上。DASPO可能成为新的生物标志物和治疗靶点。图形抽象

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来源期刊

Amino Acids 生物-生化与分子生物学

CiteScore

6.40

自引率

5.70%

发文量

审稿时长

2.2 months

期刊介绍： Amino Acids publishes contributions from all fields of amino acid and protein research: analysis, separation, synthesis, biosynthesis, cross linking amino acids, racemization/enantiomers, modification of amino acids as phosphorylation, methylation, acetylation, glycosylation and nonenzymatic glycosylation, new roles for amino acids in physiology and pathophysiology, biology, amino acid analogues and derivatives, polyamines, radiated amino acids, peptides, stable isotopes and isotopes of amino acids. Applications in medicine, food chemistry, nutrition, gastroenterology, nephrology, neurochemistry, pharmacology, excitatory amino acids are just some of the topics covered. Fields of interest include: Biochemistry, food chemistry, nutrition, neurology, psychiatry, pharmacology, nephrology, gastroenterology, microbiology