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甲硫氨酸代谢轴关键酶在多发性骨髓瘤中的作用OACSTPCD

The role of the key enzymes of methionine metabolism axis in multiple myeloma

中文摘要英文摘要

目的 探讨甲硫氨酸代谢轴是否可作为多发性骨髓瘤(MM)潜在治疗靶点.方法 选取血液内科就诊的10例多发性骨髓瘤患者(新诊断MM组与治疗反应MM组),另外选择同期在广东医科大学附属医院自愿捐献骨髓上清液的健康者5例(Ctrl组).采用超高效液相色谱质谱联用技术(UPLC-MS/MS)对3组人群骨髓上清液进行靶向定量代谢组学分析;利用代谢组学数据进行多变量统计分析.分析NCBI GEO数据库中人类MM相关高通量基因芯片数据,利用在线工具Cell Ranger和Seurat软件、生物信息工程分析技术筛选芯片数据中共同的差异基因,筛选MM中甲硫氨酸代谢轴相关的发病关键基因.结果 检测骨髓上清液发现MM患者中甲硫氨酸和半胱氨酸水平显著升高(P<0.05).筛选出参与甲硫氨酸循环的酶有甲硫氨酸腺苷转移酶2A(MAT2A)、腺苷同型半胱氨酸酶(AHCY)和精氨酸甲基转移酶1(PRMT1),发现与MM进展相关.结论 MAT2A、AHCY和PRMT1这些关键酶可能通过调节甲硫氨酸代谢,影响MM的生物学行为和疾病进程.

Objective To investigate whether methionine metabolic axis could be a potential therapeutic target for multiple myeloma(MM).Methods Ten MM patients(newly diagnosed and treatment-responsive groups)were se-lected from the Department of Hematology,and five healthy individuals who voluntarily donated bone marrow supernatant from the Affiliated Hospital of Guangdong Medical University were chosen as the control group.Targeted quantitative metabolomics analysis of bone marrow supernatants from the three groups was performed using ultra-high performance liq-uid chromatography-tandem mass spectrometry(UPLC-MS/MS).Multivariate statistical analysis was conducted on the metabolomics data.Human MM-related high-throughput gene chip data from the NCBI GEO database were analyzed using online tools Cell Ranger and Seurat software,and bioinformatics analysis techniques were used to identify common differential genes.Key genes related to the methionine metabolism axis in MM were screened.Results The levels of me-thionine and cysteine in the bone marrow supernatants of MM patients were significantly elevated(P<0.05).Enzymes involved in the methionine cycle,including methionine adenosyltransferase 2A(MAT2A),adenosylhomocysteinase(AH-CY),and protein arginine methyltransferase 1(PRMT1),were found to be associated with MM progression.Conclusion The key enzymes MAT2A,AHCY,and PRMT1 may influence the biological behavior and disease progression of MM by regulating methionine metabolism.

袁鑫;赵国鑫;岑玉蓉;郝嘉懿;李宁;冯锦山;黄金棋;何红华

广东医科大学第一临床医学院(广东湛江 524023)广东医科大学附属医院血液内科(广东湛江 524001)广州市第一人民医院血液内科(广东广州 510180)

临床医学

多发性骨髓瘤甲硫氨酸循环生物信息学甲硫氨酸腺苷转移酶2A腺苷同型半胱氨酸酶

multiple myelomamethionine cyclebioinformaticsmethionine adenosyltransferase 2Aadenosyl-homocysteinase

《广东医学》 2024 (006)

698-705 / 8

国家自然科学基金资助项目(82270143);广东省基础与应用基础研究基金资助项目(2022A1515220122);湛江市科技计划项目(2022A01019)

10.13820/j.cnki.gdyx.20240150

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