Inhibition of breast cancer growth via miR-7 suppressing ALDH1A3 activity concomitant with decreasing breast cancer stem cell subpopulation

J Cell Physiol. 2020 Feb;235(2):1405-1416. doi: 10.1002/jcp.29059. Epub 2019 Jul 25.


Breast cancer patients with high expression of aldehyde dehydrogenases (ALDHs) cell population have higher tolerability to chemotherapy since the cells posses a characteristic of breast cancer stem cells (BCSCs) that are resistant to conventional chemotherapy. In this study, we found that the ALDH-positive cells were higher in CD44+ CD24- and CD44+ CD24- ESA+ BCSCs than that in both BT549 and MDA-MB-231 cell lines but microRNA-7 (miR-7) level was lower in CD44+ CD24- and CD44+ CD24- ESA+ BCSCs than that in MDA-MB-231 cells. Moreover, miR-7 overexpression in MDA-MB-231 cells decreased ALDH1A3 activity by miR-7 directly binding to the 3'-untranslated region of ALDH1A3; while the ALDH1A3 expression was downregulated in MDA-MB-231 cells, the expressions of CD44 and Epithelium Specific Antigen (ESA) were reduced along with decreasing the BCSC subpopulation. Significantly, enforced expression of miR-7 in CD44+ CD24- ESA+ BCSC markedly inhibited the BCSC-driven xenograft growth in mice by decreasing an expression of ALDH1A3. Collectively, the findings demonstrate the miR-7 inhibits breast cancer growth via suppressing ALDH1A3 activity concomitant with decreasing BCSC subpopulation. This approach may be considered for an investigation on clinical treatment of breast cancers.

Keywords: ALDH1A3; breast cancer; cancer stem cells; miR-7; subpopulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Dehydrogenase / metabolism
  • Aldehyde Oxidoreductases / genetics*
  • Animals
  • Breast / metabolism
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Female
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • Neoplastic Stem Cells / metabolism*
  • Xenograft Model Antitumor Assays / methods


  • MIRN7 microRNA, human
  • MicroRNAs
  • Aldehyde Oxidoreductases
  • Aldehyde Dehydrogenase
  • aldehyde dehydrogenase (NAD(P)+)