MicroRNA-501-3p restricts prostate cancer growth through regulating cell cycle-related and expression-elevated protein in tumor/cyclin D1 signaling

Biochem Biophys Res Commun. 2019 Feb 12;509(3):746-752. doi: 10.1016/j.bbrc.2018.12.176. Epub 2019 Jan 6.


MicroRNA-501-3p (miR-501-3p) has been reported as a novel cancer-related miRNA in many types of cancer. However, the precise biological function of miR-501-3p in prostate cancer remains unknown. In this study, we aimed to investigate the regulatory effect and mechanism of miR-501-3p on cell growth of prostate cancer cells. We found that miR-501-3p expression was significantly downregulated in prostate cancer tissues and cell lines. Gain-of-function experiments showed that upregulation of miR-501-3p expression significantly decreased cell proliferation and colony formation, and induced cell cycle arrest in the G0/G1 phase. Bioinformatics analysis predicted that cell cycle-related and expression-elevated protein in tumor (CREPT) was a potential target gene of miR-501-3p., and the results of our luciferase reporter assay confirmed that miR-501-3p bound to the 3'-untranslated region of CREPT at the predicted binding site. Moreover, miR-501-3p was shown to negatively regulate CREPT expression in prostate cancer cells. Correlation analysis showed that miR-501-3p was inversely correlated with CREPT expression in prostate cancer tissues. Knockdown studies revealed that miR-501-3p regulated the expression of cyclin D1 by targeting CREPT. Additionally, the inhibitory effect of miR-501-3p on prostate cancer cell growth was partially reversed by CREPT overexpression. Overall, these results suggest that miR-501-3p restricts prostate cancer cell growth by targeting CREPT to inhibit the expression of cyclin D1. These findings indicate that the miR-501-3p/CREPT/cyclin D1 axis plays a crucial role in the progression of prostate cancer and may serve as potential therapeutic target.

Keywords: CREPT; Cyclin D1; Prostate cancer; miR-501–3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin D1 / genetics*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Neoplasm Proteins / genetics
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology


  • CCND1 protein, human
  • Cell Cycle Proteins
  • MIRN501 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RPRD1B protein, human
  • Cyclin D1