Lactate Dehydrogenase-A-Forming LDH5 Promotes Breast Cancer Progression
Tianxing Fang,1– 4 Liyu Hu,5 Tianshun Chen,4 Fei Li,6 Liu Yang,4 Bin Liang,7 Wenjun Wang,8 Fancai Zeng4 1Department of Nuclear Medicine, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan...
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Dove Medical Press
2025-02-01
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| Series: | Breast Cancer: Targets and Therapy |
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| Online Access: | https://www.dovepress.com/lactate-dehydrogenase-a-forming-ldh5-promotes-breast-cancer-progressio-peer-reviewed-fulltext-article-BCTT |
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| author | Fang T Hu L Chen T Li F Yang L Liang B Wang W Zeng F |
| author_facet | Fang T Hu L Chen T Li F Yang L Liang B Wang W Zeng F |
| author_sort | Fang T |
| collection | DOAJ |
| description | Tianxing Fang,1– 4 Liyu Hu,5 Tianshun Chen,4 Fei Li,6 Liu Yang,4 Bin Liang,7 Wenjun Wang,8 Fancai Zeng4 1Department of Nuclear Medicine, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan, People’s Republic of China; 3Institute of Nuclear Medicine, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 4Laboratory of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Oral & Maxillofacial Reconstruction and Regeneration of Luzhou Key Laboratory, The Affiliated Stomatological Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 6Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 7Department of General Surgery (Breast Surgery), the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 8Institute for Cancer Medicine and School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, People’s Republic of ChinaCorrespondence: Fancai Zeng; Wenjun Wang, Email zfcai@swmu.edu.cn; wenjunwang1213@126.comBackground: 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.Keywords: LDHA, LDH5 isoenzyme, breast cancer, progression, prognosis |
| format | Article |
| id | doaj-art-7be3d97086c7440a817d9897e534f30f |
| institution | Kabale University |
| issn | 1179-1314 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Breast Cancer: Targets and Therapy |
| spelling | doaj-art-7be3d97086c7440a817d9897e534f30f2025-02-11T17:30:56ZengDove Medical PressBreast Cancer: Targets and Therapy1179-13142025-02-01Volume 17157170100095Lactate Dehydrogenase-A-Forming LDH5 Promotes Breast Cancer ProgressionFang THu LChen TLi FYang LLiang BWang WZeng FTianxing Fang,1– 4 Liyu Hu,5 Tianshun Chen,4 Fei Li,6 Liu Yang,4 Bin Liang,7 Wenjun Wang,8 Fancai Zeng4 1Department of Nuclear Medicine, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan, People’s Republic of China; 3Institute of Nuclear Medicine, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 4Laboratory of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Oral & Maxillofacial Reconstruction and Regeneration of Luzhou Key Laboratory, The Affiliated Stomatological Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 6Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 7Department of General Surgery (Breast Surgery), the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 8Institute for Cancer Medicine and School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, People’s Republic of ChinaCorrespondence: Fancai Zeng; Wenjun Wang, Email zfcai@swmu.edu.cn; wenjunwang1213@126.comBackground: 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.Keywords: LDHA, LDH5 isoenzyme, breast cancer, progression, prognosishttps://www.dovepress.com/lactate-dehydrogenase-a-forming-ldh5-promotes-breast-cancer-progressio-peer-reviewed-fulltext-article-BCTTldhaldh5 isoenzymebreast cancerprogressionprognosis |
| spellingShingle | Fang T Hu L Chen T Li F Yang L Liang B Wang W Zeng F Lactate Dehydrogenase-A-Forming LDH5 Promotes Breast Cancer Progression Breast Cancer: Targets and Therapy ldha ldh5 isoenzyme breast cancer progression prognosis |
| title | Lactate Dehydrogenase-A-Forming LDH5 Promotes Breast Cancer Progression |
| title_full | Lactate Dehydrogenase-A-Forming LDH5 Promotes Breast Cancer Progression |
| title_fullStr | Lactate Dehydrogenase-A-Forming LDH5 Promotes Breast Cancer Progression |
| title_full_unstemmed | Lactate Dehydrogenase-A-Forming LDH5 Promotes Breast Cancer Progression |
| title_short | Lactate Dehydrogenase-A-Forming LDH5 Promotes Breast Cancer Progression |
| title_sort | lactate dehydrogenase a forming ldh5 promotes breast cancer progression |
| topic | ldha ldh5 isoenzyme breast cancer progression prognosis |
| url | https://www.dovepress.com/lactate-dehydrogenase-a-forming-ldh5-promotes-breast-cancer-progressio-peer-reviewed-fulltext-article-BCTT |
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