MicroRNA-33b Inhibits Breast Cancer Metastasis by Targeting HMGA2, SALL4 and Twist1

Sci Rep. 2015 Apr 28;5:9995. doi: 10.1038/srep09995.

Abstract

MicroRNAs are a class of small noncoding RNAs that regulate gene expression post-transcriptionally either by inhibiting protein translation or by causing the degradation of target mRNAs. Current evidence indicates that miR-33b is involved in the regulation of lipid metabolism, cholesterol homeostasis, glucose metabolism and several human diseases; however, whether miR-33b contributes to the pathogenesis of human cancers and participates in the regulation of self-renewal of human cancer stem cells remains unknown. Here, we report the identification of miR-33b as a negative regulator of cell stemness and metastasis in breast cancer. Compared with paired normal breast tissues, miR-33b expression is downregulated in breast tumor samples and is inversely correlated with lymph node metastatic status. Ectopic overexpression of miR-33b in highly metastatic breast cancer cells suppresses cell self-renewal, migration and invasion in vitro and inhibits lung metastasis in vivo. Conversely, miR-33b knockdown promotes the self-renewal, migration and invasion capabilities of noncancerous mammary epithelial cells. The mechanism through which miR-33b inhibits the stemness, migration and invasion of breast cancer cells is by targeting HMGA2, SALL4 and Twist1. These data indicate that miR-33b acts as an onco-suppressive microRNA in breast cancer progression by inhibiting the stemness and metastasis of breast cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / secondary*
  • Female
  • HMGA2 Protein / genetics
  • HMGA2 Protein / metabolism*
  • Humans
  • MCF-7 Cells
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Twist-Related Protein 1 / genetics
  • Twist-Related Protein 1 / metabolism*

Substances

  • HMGA2 Protein
  • MIRN33a microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • SALL4 protein, human
  • TWIST1 protein, human
  • Transcription Factors
  • Twist-Related Protein 1