title: Tumor-suppressive microRNA-145 targets catenin δ-1 to regulate Wnt/β-catenin signaling in human colon cancer cells.
abstract: The constitutive activation of Wnt/β-catenin signaling plays a central role in colon cancer. MiR-145 was earlier identified as one of the microRNAs (miRNAs) down-regulated in colon cancer cells. However, the role of miR-145 in the Wnt/β-catenin signaling pathway is poorly understood. Here, we demonstrated that miR-145 played a pivotal role in the Wnt/β-catenin signaling pathway by perturbing the intracellular translocation of β-catenin in human colon cancer cells. The ectopic expression of miR-145 inhibited the growth of DLD-1 cells by disturbing β-catenin translocation into the nucleus, thereby leading to the down-regulation of LEF/TCF transcriptional target genes c-Myc and CyclinD1. We further demonstrated that miR-145 directly targeted catenin δ-1, contributing to the aberrant translocation of β-catenin through impaired nuclear shuttling with p21-activated kinase 4 (PAK4). These findings uncover a novel role of miR-145 in modulating intracellular translocation of β-catenin on Wnt/β-catenin signaling pathway.
authors.affiliation: United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Nami
authors.initials: N
authors.lastname: Yamada
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Noguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Mori
authors.forename: Tomoki
authors.initials: T
authors.lastname: Naoe
authors.forename: Kohji
authors.initials: K
authors.lastname: Maruo
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Akao
mesh_terms: D021581:Active Transport, Cell Nucleus; D051177:Catenins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000378:metabolism*; D019938:Cyclin D1 / Q000235:genetics; D015536:Down-Regulation; D016259:Genes, myc; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D034622:RNA Interference; D034741:RNA, Small Interfering; D038501:Tankyrases / Q000037:antagonists & inhibitors; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000235:genetics*; D051176:beta Catenin / Q000378:metabolism*; D054462:p21-Activated Kinases / Q000378:metabolism; D000095002:Delta Catenin
chemical_list: D051177:Catenins; D006575:Heterocyclic Compounds, 3-Ring; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D051153:Wnt Proteins; C544261:XAV939; D051176:beta Catenin; D019938:Cyclin D1; D038501:Tankyrases; C116367:PAK4 protein, human; D054462:p21-Activated Kinases; D000095002:Delta Catenin; C000722347:CTNND1 protein, human