title: LEF1 targeting EMT in prostate cancer invasion is mediated by miR-181a.
abstract: Lymphoid enhancer-binding factor-1 (LEF1) is a key transcription factor mediating Wnt signaling pathway. Our previous studies indicate that LEF1 is highly expressed in androgen-independent prostate cancer (PCa) and enhances invasion ability in androgen-independent PCa cells. However, the molecular mechanism of LEF1 effect on invasion remains largely unknown. Using microRNA profiling analysis comparing androgen-independent LNCaP-AI PCa cells with high levels of endogenous LEF1 to LNCaP-AI cells with LEF1 knockdown by LEF1shRNA, we found miR-181a to be increased 12.3-fold in LNCaP-AI cells. We confirmed a positive correlation between LEF1 and miR-181a expression across multiple PCa cell lines. Additionally, we showed that in PCa cells, overexpression of LEF1 increased miR-181a expression and subsequently induced EMT associated migration and invasion, whereas LEF1 knockdown decreased miR-181a expression and subsequently resulted in inhibition of EMT, migration and invasion. Mechanistically, we demonstrated by chromatin immunoprecipitation assays that LEF1 could enhance miR-181a expression via its binding to the promoter regions of hsa-miR-181a. Overall, this study identified a novel LEF1-miR-181a-EMT axis in regulation of PCa migration and invasion.
authors.affiliation: Department of Pathology, New York University School of Medicine New York, NY ; 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: Basic Science and Craniofacial Biology, New York University College of Dentistry New York, NY ; Department of Urology, New York University School of Medicine New York, NY ; Department of NYU Cancer Institute, New York University School of Medicine New York, NY.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pathology, New York University School of Medicine New York, NY.
authors.forename: Yirong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology, Northwestern University Chicago, IL.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Pathology, New York University School of Medicine New York, NY.
authors.forename: Garrett
authors.initials: G
authors.lastname: Daniels
authors.affiliation: Department of Pathology, New York University School of Medicine New York, NY.
authors.forename: Xuelin
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Department of NYU Cancer Institute, New York University School of Medicine New York, NY.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathology, Johns Hopkins University Baltimore, MD.
authors.forename: Karen
authors.initials: K
authors.lastname: Sfanos
authors.affiliation: Department of Pathology, New York University School of Medicine New York, NY.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Melamed
authors.affiliation: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pathology, New York University School of Medicine New York, NY ; Department of Urology, New York University School of Medicine New York, NY ; Department of NYU Cancer Institute, New York University School of Medicine New York, NY ; Department of New York Harbor Healthcare System, New York University School of Medicine New York, NY.
authors.forename: Peng
authors.initials: P
authors.lastname: Lee
keywords: EMT; LEF1; invasion; miR-181a; prostate cancer