miR-361-5p modulates metabolism and autophagy via the Sp1-mediated regulation of PKM2 in prostate cancer

Ling,Zhixin; Liu,Dachuang; Zhang,Guangyuan; Liang,Qing; Xiang,Ping; Xu,Yan; Han,Conghui; Tao,Tao

doi:10.3892/or.2017.5852

miR-361-5p modulates metabolism and autophagy via the Sp1-mediated regulation of PKM2 in prostate cancer

Authors:
- Zhixin Ling
- Dachuang Liu
- Guangyuan Zhang
- Qing Liang
- Ping Xiang
- Yan Xu
- Conghui Han
- Tao Tao
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Affiliations: Department of Urology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China, Department of Urology, Xuzhou Central Hospital, Xuzhou, Jiangsu 221009, P.R. China, Department of Urology, Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui 230001, P.R. China
Published online on: July 25, 2017 https://doi.org/10.3892/or.2017.5852
Pages: 1621-1628

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Abstract

Prostate cancer (PCa) is a leading cause of death among men. The dysregulation of metabolism and autophagy contributes to the progression of PCa. The transcription factor specificity protein 1 (Sp1) is implicated in the regulation of metabolism and autophagy. We confirmed that Sp1 is overexpressed in castration-resistant prostate cancer (CRPC) cells. However, the roles of Sp1 in PCa metabolism and autophagy remain unclear. Thus, in the present study, we retrieved the GSE35988 dataset from Gene Expression Omnibus (GEO) database to reinvestigate Sp1 expression and its role in PCa.We found that in PCa, Sp1 knockdown significantly inhibited cell growth, aerobic glycolysis, and hypoxia-induced autophagy, which were accompanied by an increased G1 cell cycle arrest. Pearson correlation indicated that pyruvate kinase isoenzyme type M2 (PKM2) is positively correlated with Sp1 expression. Western blot analysis demonstrated that Sp1 directly regulates PKM2; therefore, Sp1 modulates metabolism and autophagy in CRPC. Western blot analysis and luciferase reporter assay also indicated that the tumor suppressor miR-361-5p inversely regulates Sp1 by directly targeting the binding site in the 3'UTR of Sp1. miR-361-5p overexpression presented effects that are similar to Sp1 depletion in PCa. In summary, this study is the first to demonstrate that miR-361-5p suppresses the Sp1/PKM2 axis, consequently affecting the progression of PCa and the metabolism and autophagy of PCa cells. Therefore, targeting the miR-361-5p/Sp1/PKM2 pathway has considerable clinical significance in preventing the malignant progression of PCa.

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