Involvement of EZH2 in aerobic glycolysis of prostate cancer through miR-181b/HK2 axis

Tao,Tao; Chen,Ming; Jiang,Ranran; Guan,Han; Huang,Yeqing; Su,Huan; Hu,Qiang; Han,Xu; Xiao,Jun

doi:10.3892/or.2017.5430

Involvement of EZH2 in aerobic glycolysis of prostate cancer through miR-181b/HK2 axis

Authors:
- Tao Tao
- Ming Chen
- Ranran Jiang
- Han Guan
- Yeqing Huang
- Huan Su
- Qiang Hu
- Xu Han
- Jun Xiao
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Affiliations: Department of Urology, Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui 230001, P.R. China, Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu 210009, P.R. China, Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China
Published online on: February 7, 2017 https://doi.org/10.3892/or.2017.5430
Pages: 1430-1436
Copyright: © Tao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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 upregulation 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.

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