MicroRNA‐488 inhibits proliferation and glycolysis in human prostate cancer cells by regulating PFKFB3

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 Ex...

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Veröffentlicht in:FEBS open bio 2019-10, Vol.9 (10), p.1798-1807
Hauptverfasser: Wang, Jun, Li, Xiaojuan, Xiao, Zhaoming, Wang, Yu, Han, Yuefu, Li, Jun, Zhu, Weian, Leng, Qu, Wen, Yuehui, Wen, Xinqiao
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Sprache:eng
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Zusammenfassung: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. The expression and function of miR‐488 in prostate cancer (PCa) are unclear. In this study, we found that miR‐488 expression is diminished in PCa. By directly targeting the 3′UTR of 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase, isoform3 (PFKFB3) mRNA, miR‐488 downregulates the expression of PFKFB3 protein and thereby inhibits PCa cell proliferation and glycolysis.
ISSN:2211-5463
2211-5463
DOI:10.1002/2211-5463.12718