Mir-30 reduction maintains self-renewal and inhibits apoptosis in breast tumor-initiating cells

Oncogene. 2010 Jul 22;29(29):4194-204. doi: 10.1038/onc.2010.167. Epub 2010 May 24.


Accumulating evidence indicates that a sub-population of cancer cells with stem-like properties, termed tumor-initiating cells (T-ICs), exist in many different kinds of malignancies, which have a pivotal role in tumorigenesis, tumor progression, metastasis and post-treatment relapse. However, how the stem-like properties of T-ICs are regulated remains obscure. Our previous study showed that reduction of let-7 microRNA (miRNA) in breast tumor-initiating cells (BT-ICs) contributes to the maintenance of their self-renewal capacity and undifferentiated status. In this study we show the effect of mir-30 reduction on the stem-like features of BT-ICs. Similar to let-7, mir-30 is reduced in BT-ICs, and the protein level of Ubc9 (ubiquitin-conjugating enzyme 9) and ITGB3 (integrin beta3), the target genes of mir-30, is markedly upregulated. Enforced constitutive expression of mir-30 in BT-ICs inhibits their self-renewal capacity by reducing Ubc9, and induces apoptosis through silencing ITGB3. On the contrary, blocking the miRNA with a specific antisense oligonucleotide (ASO) in differentiated breast cancer cells revived their self-renewal capacity. Furthermore, ectopic expression of mir-30 in BT-IC xenografts reduces tumorigenesis and lung metastasis in nonobese diabetic/severe combined immunodeficient mice, whereas blocking mir-30 expression enhances tumorigenesis and metastasis. Together, our data suggest mir-30 as one of the important miRNAs in regulating the stem-like features of T-ICs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Breast Neoplasms / pathology*
  • CD24 Antigen / analysis
  • Cell Line, Tumor
  • Female
  • Humans
  • Hyaluronan Receptors / analysis
  • Integrin beta3 / genetics
  • Integrin beta3 / physiology
  • Lung Neoplasms / secondary
  • Mice
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Neoplastic Stem Cells / pathology*
  • Ubiquitin-Conjugating Enzymes / genetics
  • Ubiquitin-Conjugating Enzymes / physiology


  • CD24 Antigen
  • CD24 protein, human
  • CD44 protein, human
  • Hyaluronan Receptors
  • ITGB3 protein, human
  • Integrin beta3
  • MIRN30b microRNA, human
  • MicroRNAs
  • Ubiquitin-Conjugating Enzymes
  • ubiquitin-conjugating enzyme UBC9