miR-1301-3p promotes prostate cancer stem cell expansion by targeting SFRP1 and GSK3β

Biomed Pharmacother. 2018 Mar:99:369-374. doi: 10.1016/j.biopha.2018.01.086.

Abstract

Cancer stem cells promote tumor progression, drug-resistance, and relapse, and many microRNAs (miRNAs) play critical roles in the expansion of cancer stem cells. In the present study, we investigated the role of miR-1301-3p in the expansion of prostate cancer stem cells; miR-1301-3p was significantly upregulated in prostate cancer cells and tissues compared with normal prostate cells and tissues. Sphere formation and side population assays suggested that miR-1301-3p promoted the expansion of prostate cancer stem cells, and increased the expression of prostate cancer stem cell-associated genes, such as OCT4, SOX2, NANOG, CD44, KLF4, c-MYC, and MMP2. MiR-1301-3p targeted Wnt pathway inhibitors, GSK3β and SFRP1, and inhibited their expression by directly binding to their 3' untranslated regions. TOP/FOP luciferase assays suggested that miR-1301-3p activated the Wnt pathway, which was confirmed by increased β-catenin expression in the nucleus. Furthermore, the miR-1301-3p level correlated negatively with GSK3β and SFRP1 in prostate cancer tissues. In summary, we found that miR-1301-3p promoted the expansion of prostate cancer stem cells by inhibiting GSK3β and SFRP1, and activating the Wnt pathway.

Keywords: GSK3β; Prostate cancer stem cell; SFRP1; miR-1301-3p.

MeSH terms

  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Self Renewal / genetics
  • Gene Expression Regulation, Neoplastic
  • Glycogen Synthase Kinase 3 beta / metabolism*
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Kruppel-Like Factor 4
  • Male
  • Membrane Proteins / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplastic Stem Cells / metabolism*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology*
  • Wnt Signaling Pathway / genetics

Substances

  • Intercellular Signaling Peptides and Proteins
  • KLF4 protein, human
  • Kruppel-Like Factor 4
  • MIRN1301 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • SFRP1 protein, human
  • Glycogen Synthase Kinase 3 beta