Abstract

Prostate cancer (PCa) remains the second leading cause of cancer‐related death among men in the United States, and its molecular mechanism remains to be elucidated. Recent studies have suggested that microRNAs may play an important role in cancer development and progression. By analyzing the Gene Expression Omnibus dataset, we found lower expression for miR‐488 in PCa than in normal tissues. Moreover, CCK‐8, EdU, glucose uptake, and lactate secrete assays revealed that overexpression of miR‐488 in PCa cell lines PC3 and DU145 resulted in inhibition of proliferation and glycolysis. In contrast, downregulation of miR‐488 expression promoted proliferation and glycolysis in PCa cells. Using a bioinformatic approach and dual‐luciferase reporter assays, we identified 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase, isoform3 (PFKFB3), as a direct target of miR‐488. Inhibition of PFKFB3 also suppressed PCa cell glycolysis and proliferation. Our study suggests that miR‐488 inhibits PCa cell proliferation and glycolysis by targeting PFKFB3, and thus, miR‐488 may be a novel therapeutic candidate for PCa.

Highlights

  • Jun Wang1,2,3, Xiaojuan Li4, Zhaoming Xiao5, Yu Wang1, Yuefu Han6, Jun Li7, Weian Zhu7, Qu Leng7, Yuehui Wen7 and Xinqiao Wen1

  • CCK-8, EdU, glucose uptake, and lactate secrete assays revealed that overexpression of miR-488 in Prostate cancer (PCa) cell lines PC3 and DU145 resulted in inhibition of proliferation and glycolysis

  • The results showed that the expression levels of miR-488 in PCa tissues were significantly lower than those in normal prostate tissues

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Summary

Introduction

Jun Wang1,2,3 , Xiaojuan Li4, Zhaoming Xiao, Yu Wang, Yuefu Han, Jun Li7, Weian Zhu, Qu Leng, Yuehui Wen and Xinqiao Wen. Prostate cancer (PCa) remains the second leading cause of cancer-related death among men in the United States, and its molecular mechanism remains to be elucidated. Recent studies have suggested that microRNAs may play an important role in cancer development and progression. Inhibition of PFKFB3 suppressed PCa cell glycolysis and proliferation. Our study suggests that miR-488 inhibits PCa cell proliferation and glycolysis by targeting PFKFB3, and miR-488 may be a novel therapeutic candidate for PCa. Prostate cancer (PCa) is a major health problem in older men and the second leading cause of cancerrelated death in males in the United States [1]. Abbreviations CRPC, castration-resistant prostate cancer; miRNAs, microRNAs; NCBI, National Center of Biotechnology Information; PCa, prostate cancer; PFKFB3, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, isoform.

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