Nakade Yusuke, Iwata Yasunori, Harada Kenichi, Sato Yasuharu, Mita Masashi, Hamase Kenji, Konno Ryuichi, Hayashi Mayo, Kobayashi Taku, Yamamura Yuta, Toyama Tadashi, Tajima Atsushi, Wada Takashi
Department of Nephrology and Rheumatology, Kanazawa University, 13-1 Takara-Machi, Kanazawa, 920-8641, Japan.
Department of Clinical Laboratory, Kanazawa University Hospital, 13-1 Takara-Machi, Kanazawa, 920-8641, Japan.
Amino Acids. 2024 Dec 24;57(1):4. doi: 10.1007/s00726-024-03426-1.
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.
D-氨基酸代谢酶与癌症发展之间的关系仍不清楚。我们旨在使用缺乏D-氨基酸相关代谢酶的小鼠来研究这种关系。我们对缺乏这些酶约900天的小鼠进行了检查，并基于寿命、病理结果和基因表达来研究D-氨基酸代谢改变对癌症发展的影响。雌性DASPO基因敲除（DASPO）小鼠的寿命比其他组小鼠短；此外，这些小鼠在肝脏、脾脏和小肠中出现了肿瘤样肿块。做出了弥漫性大B细胞淋巴瘤（DLBCL）的病理诊断。与野生型B6小鼠相比，肝脏样本的RNA测序显示DASPO小鼠中有71个基因的表达发生了特定改变；RGS 1、MTSS1和SMARCD 1被鉴定为与DLBCL相关的基因。DASPO表达低的DLBCL患者的生存期比表达高的患者短。然而，DASPO在DLBCL发展中的作用尚不清楚。因此，未来的研究应聚焦于B细胞。DASPO可能成为癌症中的新型生物标志物和治疗靶点。
