title: MicroRNA-744 promotes prostate cancer progression through aberrantly activating Wnt/β-catenin signaling.
abstract: Accumulated evidence indicate that miR-744 functions as either tumor suppressor or oncogene in the progression of a variety of tumors, with a tumor type-specific way. However, little is known about how miR-744 impacts on the tumorigenesis of human prostate cancer. In this study, employing the analyses of microarray, qRT-PCR and re-analysis of MSKCC data, we found that CRPC tissues expressed much more miR-744 than ADPC tissues did, and the expression level of miR-744 was inversely associated with survival of CRPC patients. In vitro studies revealed that miR-744 promotes PCa cells proliferation, enhances migration, invasion; in vivo results demonstrated that silencing of miR-744 mediated by shRNA dramatically reduces PCa xenograft tumor growth. Importantly, through human gene expression array, pathway enrichment analysis and Western blot, we identified that miR-744 dramatically activated Wnt/β-catenin pathway by targeting multiple negative regulators of Wnt/β-catenin signaling, including SFRP1, GSK3β, TLE3 and NKD1. At molecular level, we further defined that NKD1 is a major functional target of miR-744. Our findings indicate that miR-744 acts as one of oncogenic factor in the progression of CRPC by recruiting a mechanism of aberrant activation of Wnt/β-catenin signaling.
authors.affiliation: Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China.|Surgical Research Center, Institute of Urology, Medical School, Nanjing, China.
authors.forename: Han
authors.initials: H
authors.lastname: Guan
authors.affiliation: Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China.|Surgical Research Center, Institute of Urology, Medical School, Nanjing, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Immunology, Bengbu Medical College, Bengbu, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China.|Surgical Research Center, Institute of Urology, Medical School, Nanjing, China.
authors.forename: Yeqing
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China.|Surgical Research Center, Institute of Urology, Medical School, Nanjing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
authors.affiliation: Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China.|Surgical Research Center, Institute of Urology, Medical School, Nanjing, China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Ling
authors.affiliation: Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China.|Surgical Research Center, Institute of Urology, Medical School, Nanjing, China.
authors.forename: Zonghao
authors.initials: Z
authors.lastname: You
authors.affiliation: Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China.|Surgical Research Center, Institute of Urology, Medical School, Nanjing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China.|Surgical Research Center, Institute of Urology, Medical School, Nanjing, China.
authors.forename: Shuqiu
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China.|Surgical Research Center, Institute of Urology, Medical School, Nanjing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China.|Surgical Research Center, Institute of Urology, Medical School, Nanjing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D056970:Co-Repressor Proteins / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D000071679:Glycogen Synthase Kinase 3 beta / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D014183:Transplantation, Heterologous; D060449:Wnt Signaling Pathway / Q000235:genetics*; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D056970:Co-Repressor Proteins; D000071679:Glycogen Synthase Kinase 3 beta; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D035683:MicroRNAs; C569733:MIRN744 microRNA, human; C449091:NKD1 protein, human; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins; C570667:TLE3 protein, human
keywords: NKD1; Wnt/β-catenin signaling; miR-744; prostate cancer; tumorigenesis