TY - JOUR
T1 - miR-10b*, a master inhibitor of the cell cycle, is down-regulated in human breast tumours
AU - Biagioni, Francesca
AU - Ben-Moshe, Noa Bossel
AU - Fontemaggi, Giulia
AU - Canu, Valeria
AU - Mori, Federica
AU - Antoniani, Barbara
AU - Di Benedetto, Benedetto, Anna
AU - Santoro, Raffaela
AU - Germoni, Sabrina
AU - De Angelis, Angelis, Fernanda
AU - Cambria, Anna
AU - Avraham, Roi
AU - Grasso, Giuseppe
AU - Strano, Sabrina
AU - Muti, Paola
AU - Mottolese, Marcella
AU - Yarden, Yosef
AU - Domany, Eytan
AU - Blandino, Giovanni
N1 - AIRC-ROC [08/30R/89]; AIRC [09/8706]; Ministero della Salute; MIUR-FIRBThis work was funded by AIRC-ROC to GB, AIRC to GB (08/30R/89), AIRC to MM (09/8706), Ministero della Salute to GB and PM, MIUR-FIRB to GB and PM.
PY - 2012/11
Y1 - 2012/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84868336859&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/emmm.201201483
DO - https://doi.org/10.1002/emmm.201201483
M3 - مقالة
SN - 1757-4676
VL - 4
SP - 1214
EP - 1229
JO - EMBO Molecular Medicine
JF - EMBO Molecular Medicine
IS - 11
ER -