title: miR-125b is methylated and functions as a tumor suppressor by regulating the ETS1 proto-oncogene in human invasive breast cancer.
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.
authors: State Key Laboratory of Oncology in Southern China, and Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
authors: Yan
authors: Y
authors: Zhang
authors: Li-Xu
authors: LX
authors: Yan
authors: Qi-Nian
authors: QN
authors: Wu
authors: Zi-Ming
authors: ZM
authors: Du
authors: Jing
authors: J
authors: Chen
authors: Ding-Zhun
authors: DZ
authors: Liao
authors: Ma-Yan
authors: MY
authors: Huang
authors: Jing-Hui
authors: JH
authors: Hou
authors: Qiu-Liang
authors: QL
authors: Wu
authors: Mu-Sheng
authors: MS
authors: Zeng
authors: Wen-Lin
authors: WL
authors: Huang
authors: Yi-Xin
authors: YX
authors: Zeng
authors: Jian-Yong
authors: JY
authors: Shao
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation; D005260:Female; D016193:G1 Phase; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: C494041:ETS1 protein, human; C000715470:MAS1 protein, human; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D000090063:Proto-Oncogene Mas; D050784:Proto-Oncogene Protein c-ets-1