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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2010-05-24

AUTHORS

F Yu, H Deng, H Yao, Q Liu, F Su, E Song

ABSTRACT

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 β3), 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. More... »

PAGES

4194-4204

References to SciGraph publications

  • 2009-09-04. Cancer stem cells: mirage or reality? in NATURE MEDICINE
  • 2006-12-24. SUMOylation of Tr2 orphan receptor involves Pml and fine-tunes Oct4 expression in stem cells in NATURE STRUCTURAL & MOLECULAR BIOLOGY
  • 2001-03. Sumo, ubiquitin's mysterious cousin in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2005-02-21. A role for Ubc9 in tumorigenesis in ONCOGENE
  • 2005-10-25. Anoikis in CELL DEATH & DIFFERENTIATION
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/onc.2010.167

    DOI

    http://dx.doi.org/10.1038/onc.2010.167

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1003978093

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/20498642


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