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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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  1. Home
  3. 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.
  1. Home
  3. 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.

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Effect of D-amino acid metabolic enzyme deficiency on cancer development-diffuse large B-cell lymphoma onset and gene

Yusuke Nakade1,2, Yasunori Iwata1,2, Kenichi Harada3

  • 1Department of Nephrology and Rheumatology, Kanazawa University, 13-1 Takara-Machi, Kanazawa, 920-8641, Japan.

Amino Acids
|December 24, 2024

View abstract on PubMed

Summary
This summary is machine-generated.
Keywords:
D-amino acidD-amino acid oxidaseD-aspartate oxidaseDiffuse large B-cell lymphomaSerine racemase

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Mice lacking D-amino acid oxidase pathway enzymes (DASPO) showed reduced lifespan and developed lymphoma. Low DASPO expression in human DLBCL patients correlated with poorer survival, suggesting DASPO as a potential cancer biomarker.

Area of Science:

  • Biochemistry
  • Oncology
  • Immunology

Background:

  • The role of D-amino acid (D-AA) metabolic enzymes in cancer development is not well understood.
  • Investigating D-AA metabolism offers potential insights into novel cancer biomarkers and therapeutic targets.

Purpose of the Study:

  • To explore the relationship between D-AA metabolic enzymes and cancer development.
  • To assess the impact of altered D-AA metabolism on cancer incidence, lifespan, and gene expression using knockout mice.

Main Methods:

  • Generated and analyzed mice deficient in D-AA-related metabolic enzymes (DASPO-/-) over a 900-day period.
  • Evaluated lifespan, performed pathological examinations, and conducted RNA sequencing on liver tissues.
  • Correlated DASPO gene expression with survival data in patients diagnosed with diffuse large B-cell lymphoma (DLBCL).

Main Results:

  • Female DASPO-/- mice exhibited a shortened lifespan and developed tumor-like masses in multiple organs.
  • Pathological analysis confirmed diffuse large B-cell lymphoma (DLBCL) in affected mice.
  • RNA sequencing identified 71 differentially expressed genes in DASPO-/- mice, including DLBCL-associated genes RGS1, MTSS1, and SMARCD1.
  • Lower DASPO expression in human DLBCL patients was linked to reduced survival rates.

Conclusions:

  • Altered D-AA metabolism, specifically the absence of DASPO, is associated with lymphoma development and progression.
  • DASPO may function as a potential biomarker for DLBCL prognosis.
  • Further research focusing on B cells is warranted to elucidate the precise role of DASPO in DLBCL pathogenesis and its therapeutic potential.