乳酸脱氢酶A
拉吉细胞
发病机制
乳酸脱氢酶
淋巴瘤
基因敲除
B细胞淋巴瘤
活力测定
细胞
糖酵解
细胞生长
细胞培养
癌症研究
生物
生物化学
酶
免疫学
遗传学
作者
Xiumei Feng,Jing Ren,Xunqi Zhang,Dexiao Kong,Linlin Yin,Qian Zhou,Shunye Wang,Ai Li,Yanan Guo,Sheng Wang,Xiaoli Feng,Xiaoyun Wang,Jianhua Niu,Yang Jiang,Chengyun Zheng
摘要
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.
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