title: Involvement of EZH2 in aerobic glycolysis of prostate cancer through miR-181b/HK2 axis.
abstract: Recent studies suggest that several types of tumors preferentially metabolize glucose through aerobic glycolysis, a phenomenon known as the Warburg effect. However, it remains largely unexplored whether metabolic reprogramming is involved in prostate cancer (PCa) progression. In this study, we found that histone methyltransferase enhancer of zeste homolog 2 (EZH2) dysregulated in PCa development regulated cellular growth and aerobic glycolysis through miR-181b/hexokinase 2 (HK2) axis. Aberrant expression profiles of coding RNA and microRNA were examined by two large, independent clinical prostate cancer data sets. The results indicated that EZH2 expression was elevated followed by PCa development. A set of glycometabolism-related genes were positively correlated with EZH2 expression such as HK2.The depletion of EZH2 in cell experiments inhibited PCa cell growth and aerobic glycolysis accompanying the up-regulation of miR-181b. Western blot and luciferase reporter assays showed that miR-181b inversely modulated HK2 by directly targeting the binding site within 3'-untranslated regions. Moreover, decreased miR-181b expression largely abrogated the effect of sh-EZH2 on HK2 expression and HK2-induced glucose metabolism process. Immunohistochemistry (IHC) and in situ hybridisation (ISH) analysis further revealed a significant correlation in EZH2, miR-181b and HK2 expression in nude mouse tumor xenograft. Taken together, these findings provide the first evidence that EZH2/miR-181b/HK2 pathway plays a positive role in PCa development. Targeting this aberrantly activated pathway may provide a new therapeutic strategy against PCa.
authors.affiliation: Department of Urology, Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui 230001, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
authors.affiliation: Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Ranran
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Han
authors.initials: H
authors.lastname: Guan
authors.affiliation: Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Yeqing
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Huan
authors.initials: H
authors.lastname: Su
authors.affiliation: Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Urology, Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui 230001, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xiao
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D049109:Cell Proliferation; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis / Q000502:physiology*; D006801:Humans; D007124:Immunoenzyme Techniques; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D060787:Neoplasm Grading; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; C509805:KIF2A protein, human; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D016547:Kinesins