乳酸脱氢酶在弥漫大 B 细胞淋巴瘤生长过程中的代谢作用。

IF 3 3区 医学 Q2 HEMATOLOGY Annals of Hematology Pub Date : 2024-11-06 DOI:10.1007/s00277-024-06083-2
Jialin Zhang, Qifeng Lu, Wei Liu, Na Zhou
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引用次数: 0

摘要

乳酸脱氢酶(LDHA)活化可激活肿瘤增殖、生长、侵袭和转移,从而诱导肿瘤发生。LDHA 是否会介导肿瘤新陈代谢,从而导致弥漫大 B 细胞淋巴瘤(DLBCL)的发生仍是未知数。在此,我们研究了 LDHA 在激活后如何通过肿瘤代谢来调节 DLBCL 诱导的肿瘤。我们研究了 LDHA 在 DLBCL 患者外周血单核细胞(PBMC)中的高表达。敲除 LDHA 会增加细胞凋亡,抑制 OCI-Ly1 和 OCI-Ly10 细胞的生长和迁移。我们发现,LDHA在DLBCL细胞中获得了产生乳酸的典型酶活性,并触发NAD +。此外,p-STAT5被确定为LDHA的下游靶标,p-STAT5蛋白水平的显著降低与LDHA蛋白表达的减少有关。总之,我们的研究结果确定了LDHA在DLBCL中的致癌作用,并表明LDHA可被视为一种关键的预后生物标志物和潜在的治疗靶点。
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The metabolic role of lactate dehydrogenase in the growth of diffuse large B cell lymphoma.

Lactate dehydrogenase (LDHA) activation induces tumorigenesis by activating tumor proliferation, growth, invasion, and metastasis. Whether LDHA mediates tumor metabolism that upon diffuse large B-cell lymphoma (DLBCL) occur remains unknown. Here, we investigated how LDHA adopt tumor metabolism after activation to regulate DLBCL-inducible. We investigated LDHA is highly expressed in peripheral blood mononuclear cells (PBMCs) of DLBCL patients. Knockdown of LDHA results in an increase in the apoptosis of cells, suppression of cell growth and migration in OCI-Ly1 and OCI-Ly10 cells. We show that LDHA gains a canonical enzyme activity to produce lactate and triggers NAD + in DLBCL cells. Furthermore, p-STAT5 was identified as a downstream target of LDHA, and the p-STAT5 protein level was significantly reduced related to decreased LDHA protein expression. Collectively, our findings identify the oncogenic role of LDHA in DLBCL and suggest that LDHA can be considered as a pivotal prognostic biomarker and a potential therapeutic target.

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来源期刊
Annals of Hematology
Annals of Hematology 医学-血液学
CiteScore
5.60
自引率
2.90%
发文量
304
审稿时长
2 months
期刊介绍: Annals of Hematology covers the whole spectrum of clinical and experimental hematology, hemostaseology, blood transfusion, and related aspects of medical oncology, including diagnosis and treatment of leukemias, lymphatic neoplasias and solid tumors, and transplantation of hematopoietic stem cells. Coverage includes general aspects of oncology, molecular biology and immunology as pertinent to problems of human blood disease. The journal is associated with the German Society for Hematology and Medical Oncology, and the Austrian Society for Hematology and Oncology.
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