Wild-type p53 suppresses the epithelial-mesenchymal transition and stemness in PC-3 prostate cancer cells by modulating miR‑145

Int J Oncol. 2013 Apr;42(4):1473-81. doi: 10.3892/ijo.2013.1825. Epub 2013 Feb 12.

Abstract

The principal problem arising from prostate cancer (PCa) is its propensity to metastasize to bone and the mechanism(s) need to be further elucidated. The tumor suppressor p53 plays an important role in regulating the epithelial-mesenchymal transition (EMT) and cancer cell stemness, which have been proposed to play critical roles in cancer metastasis. MiR-145, a direct target of p53, represses bone metastasis of PCa and is involved in regulating EMT and cancer cell stemness. However, it is unknown whether wild‑type p53 (WT-p53) plays a role in regulating invasion, EMT and cancer cell stemness of PCa cells and whether miR-145 mediates the function of WT-p53. In the present study, we found that ectopic expression of WT-p53 inhibited the migration and invasion, and enhanced the adhesion of p53-null PC-3 cells derived from PCa bone metastasis. Furthermore, WT-p53 suppressed the expression of the mesenchymal markers fibronectin, vimentin, N-cadherin, ZEB2 and upregulated the expression of the epithelial marker E-cadherin in PC-3 cells. Moreover, WT-p53 also suppressed colony formation, tumor sphere formation and expression of CSC markers and stemness factors including CD44, Oct4, c-Myc and Klf4 in PC-3 cells. Importantly, WT-p53 upregulated the expression of miR-145, and the inhibitory effects of WT-p53 on migration, invasion, EMT and stemness of PC-3 cells were reversed by anti-miR-145. Together, our findings demonstrate that WT-p53 suppresses migration, invasion, EMT and stemness in PC-3 cells at least partially through modulating miR-145. These results suggest that loss of WT-p53 may promote the bone metastasis of PCa at least partially through repressing miR-145 to elevate EMT and stemness of cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Differentiation / metabolism
  • Cell Adhesion
  • Cell Adhesion Molecules / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kruppel-Like Factor 4
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / physiology
  • Prostatic Neoplasms
  • Spheroids, Cellular
  • Tumor Suppressor Protein p53 / physiology*

Substances

  • Antigens, Differentiation
  • Cell Adhesion Molecules
  • KLF4 protein, human
  • Kruppel-Like Factor 4
  • MIRN145 microRNA, human
  • MicroRNAs
  • TP53 protein, human
  • Tumor Suppressor Protein p53