Dysregulation of the miR-34a-SIRT1 axis inhibits breast cancer stemness

Oncotarget. 2015 Apr 30;6(12):10432-44. doi: 10.18632/oncotarget.3394.

Abstract

Enforced expression of miR-34a eliminates cancer stem cells in some malignant tumors. Sirtuin-1 (SIRT1) is a direct target of miR-34a. Here we found low levels of miR-34a and high levels of SIRT1 in CD44+/CD24- breast cancer stem cells (BCSCs). MiR-34a overexpression and knockdown of SIRT1 decreased proportion of BSCSs and mammosphere formation. Expression of CSC markers, ALDH1, BMI1 and Nanog was decreased. In nude mice xenografts, stable expression of miR-34a and silencing of SIRT1 reduced tumor burden. Taken together, our results demonstrated that miR-34a inhibits proliferative potential of BCSCs in vitro and in vivo, at least partially by downregulating SIRT1. The miR-34a-SIRT1 axis may play role in self-renewal of BCSCs.

Keywords: CD44+/CD24− BCSCs; SIRT1; miR-34α; stemness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Female
  • Humans
  • MCF-7 Cells
  • Mice
  • Mice, Nude
  • MicroRNAs / administration & dosage*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • Random Allocation
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism*
  • Transfection
  • Xenograft Model Antitumor Assays

Substances

  • MIRN34 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • SIRT1 protein, human
  • Sirtuin 1