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- Title
MicroRNA-21 Promotes Oral Cancer Invasion via the Wnt/β-Catenin Pathway by Targeting DKK2.
- Authors
Kawakita, Akiko; Yanamoto, Souichi; Yamada, Shin-ichi; Naruse, Tomofumi; Takahashi, Hidenori; Kawasaki, Goro; Umeda, Masahiro
- 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.
- Subjects
MICRORNA; ORAL cancer; COCARCINOGENESIS; CATENINS; CANCER invasiveness; TONGUE cancer; SQUAMOUS cell carcinoma
- Publication
Pathology & Oncology Research, 2014, Vol 20, Issue 2, p253
- ISSN
1219-4956
- Publication type
Article
- DOI
10.1007/s12253-013-9689-y