Tianxing Fang, Liyu Hu, Tianshun Chen, Fei Li, Liu Yang, Bin Liang, Wenjun Wang, Fancai Zeng
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Western blot was performed to detect LDHA expression. Agarose gel electrophoresis was performed to detect the activities of LDH isoenzymes. The in vitro proliferation, migration and invasion potentials of BC cells were evaluated using MTT assays, colony formation, wound-healing assay, matrix metalloproteinase assays and transwell assays, respectively. The activities of LDH isoenzymes in serum and tissues were measured in patients with BC and healthy controls.</p><p><strong>Results: </strong>Compared to normal tissues, LDHA expression was significantly higher in BC tissues. Patients' nodal status, histological types, <i>TP53</i> mutation status and PAM50 subtypes were significant factors influencing the <i>LDHA</i> expression. By overexpressing or silencing <i>LDHA</i> gene in BT549 cells, it was confirmed that LDHA promoted cell proliferation, migration and invasion. LDH5 isoenzyme activity in patients with BC was higher than healthy controls. The increased activity of LDH5 isoenzymes was induced by overexpression of LDHA in BC. High expression of LDHA was found to be associated with poor prognosis in BC.</p><p><strong>Conclusion: </strong>LDHA plays a critical role in the progression of BC through the regulation of the activity of LDH5 isoenzyme, indicating that LDHA may serve as a valuable target for BC treatment.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"17 ","pages":"157-170"},"PeriodicalIF":3.3000,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831019/pdf/","citationCount":"0","resultStr":"{\"title\":\"Lactate Dehydrogenase-A-Forming LDH5 Promotes Breast Cancer Progression.\",\"authors\":\"Tianxing Fang, Liyu Hu, Tianshun Chen, Fei Li, Liu Yang, Bin Liang, Wenjun Wang, Fancai Zeng\",\"doi\":\"10.2147/BCTT.S502670\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Breast cancer (BC) has become the main malignant tumor threatening the health of women worldwide. Previous studies have reported that Lactate dehydrogenase-A (LDHA) has critical roles in cancer development and progression. We aimed to explore the roles of LDHA and LDH5 isoenzyme activity in BC, which provides a new insight into LDHA for the treatment of BC.</p><p><strong>Methods: </strong>The expression of LDHA in BC and its relationship with clinicopathological features were obtained from various databases including The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), Breast Cancer-Gene Expression Miner (bc-GenExMiner), TNMplot, UALCAN. The Kaplan‒Meier Plotter was used to evaluate the prognostic value of LDHA. Western blot was performed to detect LDHA expression. Agarose gel electrophoresis was performed to detect the activities of LDH isoenzymes. The in vitro proliferation, migration and invasion potentials of BC cells were evaluated using MTT assays, colony formation, wound-healing assay, matrix metalloproteinase assays and transwell assays, respectively. 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引用次数: 0
摘要
背景：乳腺癌（Breast cancer， BC）已成为世界范围内威胁妇女健康的主要恶性肿瘤。先前的研究报道乳酸脱氢酶a （LDHA）在癌症的发生和发展中起关键作用。我们旨在探讨LDHA和LDH5同工酶活性在BC中的作用，为LDHA治疗BC提供新的视角。方法：从Cancer Genome Atlas （TCGA）、Human Protein Atlas （HPA）、Breast Cancer gene expression Miner （BC - genexminer）、TNMplot、UALCAN等数据库获取乳腺癌中LDHA的表达及其与临床病理特征的关系。应用Kaplan-Meier绘图仪评价LDHA的预后价值。Western blot检测LDHA的表达。琼脂糖凝胶电泳检测LDH同工酶活性。采用MTT法、菌落形成法、创面愈合法、基质金属蛋白酶法和transwell法分别评价BC细胞的体外增殖、迁移和侵袭能力。测定了BC患者和健康对照者血清和组织中LDH同工酶的活性。结果：与正常组织相比，LDHA在BC组织中的表达明显升高。患者的淋巴结状态、组织学类型、TP53突变状态和PAM50亚型是影响LDHA表达的重要因素。通过在BT549细胞中过表达或沉默LDHA基因，证实了LDHA促进细胞增殖、迁移和侵袭。BC患者的LDH5同工酶活性高于健康对照组。LDH5同工酶活性升高是由LDHA在BC中的过度表达引起的。在BC中发现高表达的LDHA与预后不良有关。结论：LDHA通过调节LDH5同工酶的活性在BC的进展中起关键作用，提示LDHA可能是治疗BC的有价值的靶点。
Lactate Dehydrogenase-A-Forming LDH5 Promotes Breast Cancer Progression.
Background: Breast cancer (BC) has become the main malignant tumor threatening the health of women worldwide. Previous studies have reported that Lactate dehydrogenase-A (LDHA) has critical roles in cancer development and progression. We aimed to explore the roles of LDHA and LDH5 isoenzyme activity in BC, which provides a new insight into LDHA for the treatment of BC.
Methods: The expression of LDHA in BC and its relationship with clinicopathological features were obtained from various databases including The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), Breast Cancer-Gene Expression Miner (bc-GenExMiner), TNMplot, UALCAN. The Kaplan‒Meier Plotter was used to evaluate the prognostic value of LDHA. Western blot was performed to detect LDHA expression. Agarose gel electrophoresis was performed to detect the activities of LDH isoenzymes. The in vitro proliferation, migration and invasion potentials of BC cells were evaluated using MTT assays, colony formation, wound-healing assay, matrix metalloproteinase assays and transwell assays, respectively. The activities of LDH isoenzymes in serum and tissues were measured in patients with BC and healthy controls.
Results: Compared to normal tissues, LDHA expression was significantly higher in BC tissues. Patients' nodal status, histological types, TP53 mutation status and PAM50 subtypes were significant factors influencing the LDHA expression. By overexpressing or silencing LDHA gene in BT549 cells, it was confirmed that LDHA promoted cell proliferation, migration and invasion. LDH5 isoenzyme activity in patients with BC was higher than healthy controls. The increased activity of LDH5 isoenzymes was induced by overexpression of LDHA in BC. High expression of LDHA was found to be associated with poor prognosis in BC.
Conclusion: LDHA plays a critical role in the progression of BC through the regulation of the activity of LDH5 isoenzyme, indicating that LDHA may serve as a valuable target for BC treatment.
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