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

EMBO Molecular Medicine

Francesca Biagioni⁶  Noa Bossel Ben-Moshe⁵  Giulia Fontemaggi⁶  Valeria Canu⁶  Federica Mori⁷  Barbara Antoniani⁸  Anna Di Benedetto⁸  Raffaela Santoro⁷  Sabrina Germoni²  Fernanda De Angelis⁶  Anna Cambria³  Roi Avraham⁹  Giuseppe Grasso³  Sabrina Strano⁷  Paola Muti¹  Marcella Mottolese⁸  Yosef Yarden⁴  Eytan Domany⁵ 

[1] Department of Oncology, Juravinski Cancer Center McMaster University Hamilton, Ontario, Canada;SAFU Department, Regina Elena National Cancer Institute, Rome, Italy;Department of Oncology, Division of Pathology, S. Vincenzo Hospital, Taormina, Italy;Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel;Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel;Translational Oncogenomic Unit, Regina Elena National Cancer Institute, Rome, Italy;Molecular Chemoprevention Group, Regina Elena National Cancer Institute, Rome, Italy;Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy;Broad Institute of MIT and Harvard, Cambridge, MA, USA

关键词: breast cancer;    cell proliferation;    expression profiling;    microRNA;    miR‐10b*;   

DOI  :  10.1002/emmm.201201483

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY   
Copyright © 2012 EMBO Molecular Medicine

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.