MiR-34b-3 and miR-449a inhibit malignant progression of nasopharyngeal carcinoma by targeting lactate dehydrogenase A
| Autor: | Guiyuan Li, Renpeng Fang, Li Fang, Zhezhe Zhang, Zheng Li, Liqing Jia, Huiling Li, Ming Zhou, Xiaolu Ge, Jing Yang, Shuping Peng, Gaoming Xiao, Wei Xiong, Xiaoling Li, Jianpin Liu, Zhaoyang Zeng, Wen Zhou, Juanjuan Xiang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Proteomics Proteome Lactate dehydrogenase A Transplantation Heterologous Mice Nude medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation lactate dehydrogenase A(LDHA) Tandem Mass Spectrometry Cell Line Tumor microRNA Medicine Animals Humans LC-MS/MS education 3' Untranslated Regions Cell Proliferation education.field_of_study L-Lactate Dehydrogenase business.industry nasopharyngeal carcinoma miR-34b-3 Cancer Nasopharyngeal Neoplasms Transfection medicine.disease Gene expression profiling Gene Expression Regulation Neoplastic Isoenzymes MicroRNAs 030104 developmental biology Oncology Nasopharyngeal carcinoma 030220 oncology & carcinogenesis Cancer research Disease Progression miR449a Lactate Dehydrogenase 5 business Carcinogenesis Glycolysis Chromatography Liquid Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Huiling Li 1, 2 , Xiaoling Li 2 , Xiaolu Ge 2 , Liqing Jia 2 , Zhezhe Zhang 2 , Renpeng Fang 4 , Jing Yang 2 , Jianpin Liu 3 , Shuping Peng 2 , Ming Zhou 2 , Juanjuan Xiang 2 , Zhaoyang Zeng 2 , Wen Zhou 2 , Wei Xiong 2 , Gaoming Xiao 1 , Li Fang 1 , Gui-yuan Li 1, 2 , Zheng Li 1, 2, 3 1 Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China 2 The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China 3 High Resolution Mass Spectrometry Laboratory of Advanced Research Center, Central South University, Changsha, China 4 Xiangya School of Medicine, Central South University, Changsha, China Correspondence to: Zheng Li, email: lizheng@csu.edu.cn Keywords: nasopharyngeal carcinoma, miR-34b-3, miR449a, LC-MS/MS, lactate dehydrogenase A(LDHA) Received: January 19, 2016 Accepted: July 06, 2016 Published: July 21, 2016 ABSTRACT MicroRNA expression profiling assays have shown that miR-34b/c and miR-449a are down-regulated in nasopharyngeal carcinoma (NPC); however, the targets and functions of miR-34b/c and miR-449a in the pathologenesis of NPC remain elusive. In this study, we verified miR-34b/c and miR-449a were significantly reduced with the advance of NPC. Overexpression of miR-34b-3 and miR-449a suppressed the growth of NPC cells in culture and mouse tumor xenografts. Using tandem mass tags for quantitative labeling and LC-MS/MS analysis to investigate protein changes after restoring expression of miR-34b-3, 251 proteins were found to be down-regulated after miR-34b-3 transfection. Through 3 replicate experiments, we found that miR-34b-3 regulated the expression of 15 potential targeted genes mainly clustered in the key enzymes of glycolysis metabolism, including lactate dehydrogenase A (LDHA). Further investigation revealed that miR-34b-3 and miR-449a negatively regulated LDHA by binding to the 3’ untranslated regions of LDHA. Furthermore, LDHA overexpression rescued the miR-34b-3 and miR-449a induced tumor inhibition effect in CNE2 cells. In addition, miR-34b-3 and miR-449a suppressed LDH activity and reduced LD content, which were directly induced by downregulation of the LDHA. Our findings suggest that miR-34b-3 and miR-449a suppress the development of NPC through regulation of glycolysis via targeting LDHA and may be potential therapeutic targets for the treatment of NPC. |
| Databáze: | OpenAIRE |
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