Open AccessmiR‐10b*, a master inhibitor of the cell cycle, is down‐regulated in human breast tumours
Author(s) -
Biagioni Francesca,
Bossel BenMoshe Noa,
Fontemaggi Giulia,
Canu Valeria,
Mori Federica,
Antoniani Barbara,
Di Benedetto Anna,
Santoro Raffaela,
Germoni Sabrina,
De Angelis Fernanda,
Cambria Anna,
Avraham Roi,
Grasso Giuseppe,
Strano Sabrina,
Muti Paola,
Mottolese Marcella,
Yarden Yosef,
Domany Eytan,
Blandino Giovanni
Publication year - 2012
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201201483
Subject(s) - microrna , cancer research , cell growth , ectopic expression , breast cancer , cell cycle , biology , in vivo , metastasis , cancer , cell culture , biochemistry , microbiology and biotechnology , genetics , gene
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 (5 kb) 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.