title: The miR-34a-LDHA axis regulates glucose metabolism and tumor growth in breast cancer.
abstract: Lactate dehydrogenase A (LDHA) is involved in a variety of cancers. The purpose of this study was to investigate the expression, prognostic roles and function of LDHA in breast cancer. We found that LDHA was upregulated in both breast cancer cell lines and clinical specimens using quantitative real-time PCR (qRT-PCR). Immunohistochemistry (IHC) analysis of tissue microarrays (TMAs) showed that high LDHA expression was associated with cell proliferation, metastasis and poor patient overall survival (OS) and disease free survival (DFS). Furthermore, we found that LDHA promoted glycolysis and cell proliferation in vitro and in vivo. We also performed luciferase reporter assays and found that LDHA was a direct target of miR-34a. Repression of LDHA by miR-34a suppressed glycolysis and cell proliferation in breast cancer cells in vitro. Our findings provide clues regarding the role of miR-34a as a tumor suppressor in breast cancer through the inhibition of LDHA both in vitro and in vivo. Targeting LDHA through miR-34a could be a potential therapeutic strategy in breast cancer.
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Xiangsheng
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Xiaojia
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ye
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Cailu
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Jiahuai
authors.initials: J
authors.lastname: Wen
authors.affiliation: Cancer Center of Guangzhou Medical University, Cancer Research Institute of Guangzhou Medical University, Guangzhou Key Laboratory of Translational Medicine on Malignant Tumor Treatment, Guangzhou, 510060, China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Cancer Center of Guangzhou Medical University, Cancer Research Institute of Guangzhou Medical University, Guangzhou Key Laboratory of Translational Medicine on Malignant Tumor Treatment, Guangzhou, 510060, China.
authors.forename: Guopei
authors.initials: G
authors.lastname: Zheng
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Hailin
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xie
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000235:genetics*; D006801:Humans; D007279:Injections, Subcutaneous; D045022:Lactate Dehydrogenases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction; D016019:Survival Analysis
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D045022:Lactate Dehydrogenases; C071195:D-lactate dehydrogenase; D008156:Luciferases; D005947:Glucose