Data di Pubblicazione:
2012
Citazione:
miR-10b*, a master inhibitor of the cell cycle, is down-regulated in human breast tumours / F. Biagioni, N. Bossel Ben-Moshe, G. Fontemaggi, V. Canu, F. Mori, B. Antoniani, A. Di Benedetto, R. Santoro, S. Germoni, F. De Angelis, A. Cambria, R. Avraham, G. Grasso, S. Strano, P. Muti, M. Mottolese, Y. Yarden, E. Domany, G. Blandino. - In: EMBO MOLECULAR MEDICINE. - ISSN 1757-4676. - 4:11(2012), pp. 1214-1229. [10.1002/emmm.201201483]
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Breast cancer; Cell proliferation; Expression profiling; MicroRNA; MiR-10b; Animals; Breast Neoplasms; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Cyclin A2; DNA Methylation; Female; Gene Expression Regulation, Neoplastic; Humans; Mice; Mice, SCID; MicroRNAs; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins; Cell Cycle; Down-Regulation
Elenco autori:
F. Biagioni, N. Bossel Ben-Moshe, G. Fontemaggi, V. Canu, F. Mori, B. Antoniani, A. Di Benedetto, R. Santoro, S. Germoni, F. De Angelis, A. Cambria, R. Avraham, G. Grasso, S. Strano, P. Muti, M. Mottolese, Y. Yarden, E. Domany, G. Blandino
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