title: miR-10b*, a master inhibitor of the cell cycle, is down-regulated in human breast tumours.
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 (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.
authors.affiliation: Translational Oncogenomic Unit, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Biagioni
authors.forename: Noa
authors.initials: N
authors.lastname: Bossel Ben-Moshe
authors.forename: Giulia
authors.initials: G
authors.lastname: Fontemaggi
authors.forename: Valeria
authors.initials: V
authors.lastname: Canu
authors.forename: Federica
authors.initials: F
authors.lastname: Mori
authors.forename: Barbara
authors.initials: B
authors.lastname: Antoniani
authors.forename: Anna
authors.initials: A
authors.lastname: Di Benedetto
authors.forename: Raffaela
authors.initials: R
authors.lastname: Santoro
authors.forename: Sabrina
authors.initials: S
authors.lastname: Germoni
authors.forename: Fernanda
authors.initials: F
authors.lastname: De Angelis
authors.forename: Anna
authors.initials: A
authors.lastname: Cambria
authors.forename: Roi
authors.initials: R
authors.lastname: Avraham
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Grasso
authors.forename: Sabrina
authors.initials: S
authors.lastname: Strano
authors.forename: Paola
authors.initials: P
authors.lastname: Muti
authors.forename: Marcella
authors.initials: M
authors.lastname: Mottolese
authors.forename: Yosef
authors.initials: Y
authors.lastname: Yarden
authors.forename: Eytan
authors.initials: E
authors.lastname: Domany
authors.forename: Giovanni
authors.initials: G
authors.lastname: Blandino
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D056751:Cyclin A2 / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D056751:Cyclin A2; D035683:MicroRNAs; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C503721:CCNA2 protein, human; C547183:MIRN10 microRNA, human; C584277:BUB1 protein, human; C584281:Bub1 protein, mouse; C090464:Bub1 spindle checkpoint protein