title: MicroRNA-21 promotes oral cancer invasion via the Wnt/β-catenin pathway by targeting DKK2.
abstract: MicroRNA-21 (miR-21) is overexpressed in a wide variety of cancers and has been related to cellular proliferation, apoptosis, and invasion; however, the function of miR-21 is unknown in oral tongue squamous cell carcinoma (OTSCC). The purpose of this study was to examine miR-21 expression in OTSCC, correlate it with clinicopathological factors, and investigate its contribution to OTSCC cell invasion. MiR-21 expression in 79 primary OTSCCs was evaluated using locked nucleic acid in situ hybridization, and correlation was examined with the clinicopathological factors. To determine the miR-21 target, we searched for molecular genes involved in tumor invasion using the commonly cited prediction program miRanda. In an OTSCC cell line, SCC25 cells, we further evaluated whether miR-21 contributes to cell invasiveness by blocking its expression with a specific knockdown LNA probe and confirmed the direct target by Matrigel invasion assay and Western blotting. MiR-21 overexpression was detected in 60 of 79 cases (75.9 %) and correlated with the pattern of invasion (P = 0.016). We selected DKK2 as a Wnt/antagonist involved in tumor invasion. MiR-21 overexpression was significantly correlated with the DKK2-/β-catenin- immunohistochemical phenotype. Knockdown of miR-21 significantly decreased the invasion potential of SCC25 cells with up-regulated DKK2. It was found that miR-21 is overexpressed and associated with tumor invasion in OTSCC, and that miR-21 promotes OTSCC cell invasion via the Wnt/β-catenin pathway by targeting DKK2 in vitro. These results suggest that miR-21 may be a potential therapeutic target for OTSCC treatment.
authors.affiliation: Department of Clinical Oral Oncology, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8588, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kawakita
authors.forename: Souichi
authors.initials: S
authors.lastname: Yanamoto
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Yamada
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Naruse
authors.forename: Hidenori
authors.initials: H
authors.lastname: Takahashi
authors.forename: Goro
authors.initials: G
authors.lastname: Kawasaki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Umeda
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics*
chemical_list: C498622:DKK2 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D051153:Wnt Proteins; D051176:beta Catenin