Distinct microRNA expression profiles in prostate cancer stem/progenitor cells and tumor-suppressive functions of let-7

Cancer Res. 2012 Jul 1;72(13):3393-404. doi: 10.1158/0008-5472.CAN-11-3864. Epub 2012 Jun 19.

Abstract

MiRNAs regulate cancer cells, but their potential effects on cancer stem/progenitor cells are still being explored. In this study, we used quantitative real-time-PCR to define miRNA expression patterns in various stem/progenitor cell populations in prostate cancer, including CD44+, CD133+, integrin α2β1+, and side population cells. We identified distinct and common patterns in these different tumorigenic cell subsets. Multiple tumor-suppressive miRNAs were downregulated coordinately in several prostate cancer stem/progenitor cell populations, namely, miR-34a, let-7b, miR-106a, and miR-141, whereas miR-301 and miR-452 were commonly overexpressed. The let-7 overexpression inhibited prostate cancer cell proliferation and clonal expansion in vitro and tumor regeneration in vivo. In addition, let-7 and miR-34a exerted differential inhibitory effects in prostate cancer cells, with miR-34a inducing G1 phase cell-cycle arrest accompanied by cell senescence and let-7 inducing G2-M phase cell-cycle arrest without senescence. Taken together, our findings define distinct miRNA expression patterns that coordinately regulate the tumorigenicity of prostate cancer cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Gene Expression Profiling*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / physiology
  • Neoplastic Stem Cells / pathology*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology

Substances

  • MicroRNAs
  • mirnlet7 microRNA, human