1. Academic Validation
  2. Lactate dehydrogenase A is implicated in the pathogenesis of B-cell lymphoma through regulation of the FER signaling pathway

Lactate dehydrogenase A is implicated in the pathogenesis of B-cell lymphoma through regulation of the FER signaling pathway

  • Biofactors. 2024 Mar 22. doi: 10.1002/biof.2053.
Xiumei Feng 1 2 Jing Ren 3 Xunqi Zhang 1 Dexiao Kong 1 Linlin Yin 2 Qian Zhou 4 Shunye Wang 1 Ai Li 1 Yanan Guo 1 Yongjing Wang 1 Xiaoli Feng 5 Xiaoyun Wang 6 Jianhua Niu 2 Yang Jiang 1 Chengyun Zheng 1
Affiliations

Affiliations

  • 1 Department of Hematology, The Second Hospital of Shandong University, Jinan, China.
  • 2 Department of Hematology, Fourth People's Hospital of Jinan City, Jinan, China.
  • 3 Department of Hematology, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.
  • 4 Hematology Department, Linyi Central Hospital, Yishui, China.
  • 5 Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, China.
  • 6 Department of Nursing, The Second Hospital of Shandong University, Jinan, China.
Abstract

Lactate Dehydrogenase A (LDHA) is highly expressed in various tumors. However, the role of LDHA in the pathogenesis of B-cell lymphoma remains unclear. Analysis of data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases revealed an elevated LDHA expression in diffuse large B-cell lymphoma (DLBC) tissues compared with normal tissues. Similarly, our results demonstrated a significant increase in LDHA expression in tumor tissues from the patients with B-cell lymphoma compared with those with lymphadenitis. To further elucidate potential roles of LDHA in B-cell lymphoma pathogenesis, we silenced LDHA in the Raji cells (a B-cell lymphoma cell line) using shRNA techniques. Silencing LDHA led to reduced mitochondrial membrane integrity, adenosine triphosphate (ATP) production, glycolytic activity, cell viability and invasion. Notably, LDHA knockdown substantially suppressed in vivo growth of Raji cells and extended survival in mice bearing lymphoma (Raji cells). Moreover, proteomic analysis identified feline sarcoma-related protein (FER) as a differential protein positively associated with LDHA expression. Treatment with E260, a FER inhibitor, significantly reduced the metabolism, proliferation and invasion of Raji cells. In summary, our findings highlight that LDHA plays multiple roles in B-cell lymphoma pathogenesis via FER pathways, establishing LDHA/FER may as a potential therapeutic target.

Keywords

B‐cell lymphoma; LDHA; invasion; metabolism; proliferation.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-112097
    99.05%, Fer/FerT Inhibitor