miR-10b*, a master inhibitor of the cell cycle, is down-regulated in human breast tumours

Francesca Biagioni, Noa Bossel Ben-Moshe, Giulia Fontemaggi, Valeria Canu, Federica Mori, Barbara Antoniani, Anna Di Benedetto, Raffaela Santoro, Sabrina Germoni, Fernanda De Angelis, Anna Cambria, Roi Avraham, Giuseppe Grasso, Sabrina Strano, Paola Muti, Marcella Mottolese, Yosef Yarden, Eytan Domany, Giovanni Blandino

Research output: Contribution to journalArticlepeer-review

Abstract

Deregulated proliferation is a hallmark of cancer cells. Here, we show that microRNA-10b* is a master regulator of breast cancer cell proliferation and is downregulated in tumoural samples versus matched peritumoural counterparts. Two canonical CpG islands (5kb) upstream from the precursor sequence are hypermethylated in the analysed breast cancer tissues. Ectopic delivery of synthetic microRNA-10b* in breast cancer cell lines or into xenograft mouse breast tumours inhibits cell proliferation and impairs tumour growth in vivo, respectively. We identified and validated in vitro and in vivo three novel target mRNAs of miR-10b* (BUB1, PLK1 and CCNA2), which play a remarkable role in cell cycle regulation and whose high expression in breast cancer patients is associated with reduced disease-free survival, relapse-free survival and metastasis-free survival when compared to patients with low expression. This also suggests that restoration of microRNA-10b* expression might have therapeutic promise.

Original languageEnglish
Pages (from-to)1214-1229
Number of pages16
JournalEMBO Molecular Medicine
Volume4
Issue number11
DOIs
Publication statusPublished - Nov 2012

Keywords

  • Breast cancer
  • Cell proliferation
  • Expression profiling
  • MicroRNA
  • MiR-10b

ASJC Scopus subject areas

  • Molecular Medicine

Fingerprint

Dive into the research topics of 'miR-10b*, a master inhibitor of the cell cycle, is down-regulated in human breast tumours'. Together they form a unique fingerprint.

Cite this