Year-end Sale % OFF 
Abstract
The microRNA miR-125b is dysregulated in various human cancers but its underlying mechanisms of action are poorly understood. Here, we report that miR-125b is downregulated in invasive breast cancers where it predicts poor patient survival. Hypermethylation of the miR-125b promoter partially accounted for reduction of miR-125b expression in human breast cancer. Ectopic restoration of miR-125b expression in breast cancer cells suppressed proliferation, induced G(1) cell-cycle arrest in vitro, and inhibited tumorigenesis in vivo. We identified the ETS1 gene as a novel direct target of miR-125b. siRNA-mediated ETS1 knockdown phenocopied the effect of miR-125b in breast cell lines and ETS1 overexpression in invasive breast cancer tissues also correlated with poor patient prognosis. Taken together, our findings point to an important role for miR-125b in the molecular etiology of invasive breast cancer, and they suggest miR-125b as a potential theranostic tool in this disease.
Highlights
MicroRNAs are small, noncoding RNAs that modulate gene expression by binding to the 30-untranslated region (30-UTR) of target mRNA, and promoting RNA degradation, inhibiting mRNA translation, and affecting transcription [1]
Growing evidence indicates that miRNAs play important roles in biological processes including development [2], cell proliferation, apoptosis [3], and differentiation [4]. miRNAs are aberrantly expressed or mutated in cancer, suggesting that they may function as either tumor suppressors or oncogenes [5]
A decrease in miR-125b staining intensity was observed in invasive breast cancer tissues, compared with corresponding NATs by chromogenic in situ hybridization
Summary
MicroRNAs (miRNAs) are small, noncoding RNAs that modulate gene expression by binding to the 30-untranslated region (30-UTR) of target mRNA, and promoting RNA degradation, inhibiting mRNA translation, and affecting transcription [1]. MiRNAs are aberrantly expressed or mutated in cancer, suggesting that they may function as either tumor suppressors or oncogenes [5]. MiR-125b, a brain-enriched miRNA, is evenly distributed between neurons and astrocytes [6]. Recent reports suggest that miR-125b might act as an oncogene or as a tumor suppressor, depending on the cellular context. Deregulation of miR-125b has been observed in invasive breast cancer, Authors' Affiliations: 1State Key Laboratory of Oncology in Southern China, and Department of Pathology, Sun Yat-sen University Cancer Center; 2State Key Laboratory of Oncology in Southern China, and Department of Experiment Research, Sun Yat-sen University Cancer Center, Guangzhou, PR China; and 3Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden. Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
