{"title":"乳酸脱氢酶 A 通过调节 FER 信号通路与 B 细胞淋巴瘤的发病机制有关。","authors":"Xiumei Feng, Jing Ren, Xunqi Zhang, Dexiao Kong, Linlin Yin, Qian Zhou, Shunye Wang, Ai Li, Yanan Guo, Yongjing Wang, Xiaoli Feng, Xiaoyun Wang, Jianhua Niu, Yang Jiang, Chengyun Zheng","doi":"10.1002/biof.2053","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"50 5","pages":"1024-1038"},"PeriodicalIF":5.0000,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Lactate dehydrogenase A is implicated in the pathogenesis of B-cell lymphoma through regulation of the FER signaling pathway\",\"authors\":\"Xiumei Feng, Jing Ren, Xunqi Zhang, Dexiao Kong, Linlin Yin, Qian Zhou, Shunye Wang, Ai Li, Yanan Guo, Yongjing Wang, Xiaoli Feng, Xiaoyun Wang, Jianhua Niu, Yang Jiang, Chengyun Zheng\",\"doi\":\"10.1002/biof.2053\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>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.</p>\",\"PeriodicalId\":8923,\"journal\":{\"name\":\"BioFactors\",\"volume\":\"50 5\",\"pages\":\"1024-1038\"},\"PeriodicalIF\":5.0000,\"publicationDate\":\"2024-03-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BioFactors\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/biof.2053\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BioFactors","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/biof.2053","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
乳酸脱氢酶A(LDHA)在多种肿瘤中高度表达。然而,LDHA在B细胞淋巴瘤发病机制中的作用仍不清楚。癌症基因组图谱(TCGA)和基因型-组织表达(GTEx)数据库的数据分析显示,与正常组织相比,弥漫大B细胞淋巴瘤(DLBC)组织中的LDHA表达升高。同样,我们的研究结果表明,与淋巴结炎患者相比,LDHA在B细胞淋巴瘤患者肿瘤组织中的表达显著增加。为了进一步阐明 LDHA 在 B 细胞淋巴瘤发病机制中的潜在作用,我们利用 shRNA 技术在 Raji 细胞(一种 B 细胞淋巴瘤细胞系)中沉默了 LDHA。沉默LDHA会导致线粒体膜完整性、三磷酸腺苷(ATP)生成、糖酵解活性、细胞活力和侵袭性降低。值得注意的是,LDHA 基因敲除大大抑制了 Raji 细胞在体内的生长,并延长了携带淋巴瘤(Raji 细胞)的小鼠的存活时间。此外,蛋白质组分析发现猫肉瘤相关蛋白(FER)是一种与 LDHA 表达正相关的差异蛋白。用 FER 抑制剂 E260 治疗可显著降低 Raji 细胞的代谢、增殖和侵袭。总之,我们的研究结果突出表明,LDHA通过FER通路在B细胞淋巴瘤发病机制中发挥多种作用,从而确立了LDHA/FER可能成为潜在的治疗靶点。
Lactate dehydrogenase A is implicated in the pathogenesis of B-cell lymphoma through regulation of the FER signaling pathway
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.
期刊介绍:
BioFactors, a journal of the International Union of Biochemistry and Molecular Biology, is devoted to the rapid publication of highly significant original research articles and reviews in experimental biology in health and disease.
The word “biofactors” refers to the many compounds that regulate biological functions. Biological factors comprise many molecules produced or modified by living organisms, and present in many essential systems like the blood, the nervous or immunological systems. A non-exhaustive list of biological factors includes neurotransmitters, cytokines, chemokines, hormones, coagulation factors, transcription factors, signaling molecules, receptor ligands and many more. In the group of biofactors we can accommodate several classical molecules not synthetized in the body such as vitamins, micronutrients or essential trace elements.
In keeping with this unified view of biochemistry, BioFactors publishes research dealing with the identification of new substances and the elucidation of their functions at the biophysical, biochemical, cellular and human level as well as studies revealing novel functions of already known biofactors. The journal encourages the submission of studies that use biochemistry, biophysics, cell and molecular biology and/or cell signaling approaches.