title: LEF1 Targeting EMT in Prostate Cancer Invasion Is Regulated by miR-34a.
abstract: The microRNA-34a (miR-34a), a tumor-suppressive microRNA (miRNA), is implicated in epithelial-mesenchymal transition (EMT) and cancer stem cells. Lymphoid enhancer-binding factor-1 (LEF1) is a key transcription factor in the Wnt signaling pathway, and has been suggested to be involved in regulation of cell proliferation and invasion. Here, the molecular mechanism of miR-34a and LEF1 in cooperatively regulating prostate cancer cell invasion is described. Molecular profiling analysis of miRNA levels in prostate cancer cells revealed a negative correlation between miR-34a and LEF1 expression, and the downregulation of LEF1 by miR-34a was confirmed by luciferase assays. Furthermore, miR-34a specifically repressed LEF1 expression through direct binding to its 3'-untranslated regions (3'-UTR). miR-34a modulated the levels of LEF1 to regulate EMT in prostate cancer cells. Functionally, miR-34a negatively correlated with the migration and invasion of prostate cancer cells through LEF1. An analysis of miR-34a expression levels in matched human tumor and benign tissues demonstrated consistent and statistically significant downregulation of miR-34a in primary prostate cancer specimens. These data strongly suggest that miR-34a/LEF1 regulation of EMT plays an important role in prostate cancer migration and invasion.
  
  
  CONCLUSIONS
  The miR-34a-LEF1 axis represents a potential molecular target for novel therapeutic strategies in prostate cancer.
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, New York. Department of Urology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jiaqian
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, New York.
authors.forename: Yirong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, New York.
authors.forename: Garrett
authors.initials: G
authors.lastname: Daniels
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Karen
authors.initials: K
authors.lastname: Sfanos
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Angelo
authors.initials: A
authors.lastname: De Marzo
authors.affiliation: Department of Pathology, Northwestern University, Chicago, Illinois.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Wei
authors.affiliation: NYU Cancer Institute, New York University School of Medicine, New York, New York. Department of Urology, New York University School of Medicine, New York, New York. Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, New York.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Pediatric Lab of Medical Science Experiment Center, Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Chen
authors.affiliation: NYU Cancer Institute, New York University School of Medicine, New York, New York.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, New York.
authors.forename: Xuelin
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, New York.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Melamed
authors.affiliation: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. peng.lee@nyumc.org Zhaojun21@yahoo.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, New York. NYU Cancer Institute, New York University School of Medicine, New York, New York. Department of Urology, New York University School of Medicine, New York, New York. New York Harbor Healthcare System, New York University School of Medicine, New York, New York. peng.lee@nyumc.org Zhaojun21@yahoo.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Lee
mesh_terms: D020413:3' Untranslated Regions; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D020413:3' Untranslated Regions; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; C522425:MIRN34 microRNA, human; D035683:MicroRNAs