MicroRNA-21 Promotes Oral Cancer Invasion via the Wnt/β-Catenin Pathway by Targeting DKK2

• DOI: 10.1007/s12253-013-9689-y
• Publication Date: 2013-09-02T17:50:34Z
• Authors: Akiko Kawakita; Souichi Yanamoto; Shin-ichi Yamada; Tomofumi Naruse; Hidenori Takahashi; Goro Kawasaki; Masahiro Umeda
• Keywords: Male; 0303 health sciences; Up-Regulation; 3. Good health; Gene Expression Regulation, Neoplastic; Wnt Proteins; MicroRNAs; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; Humans; Intercellular Signaling Peptides and Proteins; Female; Mouth Neoplasms; Neoplasm Invasiveness; beta Catenin; Aged; Cell Proliferation

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.