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乳酸脱氢酶在弥漫性大B细胞淋巴瘤生长中的代谢作用。

The metabolic role of lactate dehydrogenase in the growth of diffuse large B cell lymphoma.

作者信息

Zhang Jialin, Lu Qifeng, Liu Wei, Zhou Na

机构信息

Department of Endocrinology, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250013, China.

Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.

出版信息

Ann Hematol. 2025 Jan;104(1):545-558. doi: 10.1007/s00277-024-06083-2. Epub 2024 Nov 6.

Abstract

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.

摘要

乳酸脱氢酶A(LDHA)激活通过促进肿瘤增殖、生长、侵袭和转移来诱导肿瘤发生。LDHA是否介导弥漫性大B细胞淋巴瘤(DLBCL)发生时的肿瘤代谢仍不清楚。在此,我们研究了LDHA激活后如何采用肿瘤代谢来调节DLBCL诱导。我们研究发现LDHA在DLBCL患者外周血单核细胞(PBMC)中高表达。敲低LDHA导致OCI-Ly1和OCI-Ly10细胞凋亡增加、细胞生长和迁移受到抑制。我们表明,LDHA在DLBCL细胞中获得了产生乳酸并触发NAD+的典型酶活性。此外,p-STAT5被鉴定为LDHA的下游靶点,并且与LDHA蛋白表达降低相关,p-STAT5蛋白水平显著降低。总体而言,我们的研究结果确定了LDHA在DLBCL中的致癌作用,并表明LDHA可被视为关键的预后生物标志物和潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f93c/11868233/3f78ef42e222/277_2024_6083_Fig1_HTML.jpg

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