Downregulated miR329 and miR410 Promote the Proliferation and Invasion of Oral Squamous Cell Carcinoma by Targeting Wnt-7b

Abstract

microRNA (miRNA) dysregulation contributes widely to human cancer but has not been fully assessed in oral cancers. In this study, we conducted a global microarray analysis of miRNA expression in 40 pairs of betel quid-associated oral squamous cell carcinoma (OSCC) specimens and their matched nontumorous epithelial counterparts. Eighty-four miRNAs were differentially expressed in the OSCC specimens compared with the matched tissue. Among these downregulated miRNAs, 19 miRNAs were found and mapped to the chromosome 14q32.2 miRNA cluster region, which resides within a parentally imprinted region designated as Dlk-Dio3 and known to be important in development and growth. Bioinformatic analysis predicted two miRNAs from the cluster region, miR329 and miR410, which could potentially target Wnt-7b, an activator of the Wnt-b-catenin pathway, thereby attenuating the Wnt-b-catenin signaling pathway in OSCC. Stable ectopic expression of Wnt-7b in OSCC cells overexpressing miR329 or miR410 restored proliferation and invasion capabilities abolished by these miRNA. Combining a demethylation agent and a histone deacetylase inhibitor was sufficient to reexpress miR329, miR410, and Meg3, consistent with epigenetic regulation of these miRNA in human OSCC. Specifically, arecoline, a major betel nut alkaloid, reduced miR329, miR410, and Meg3 gene expression. Overall, our results provide novel molecular insights into how betel quid contributes to oral carcinogenesis through epigenetic silencing of tumor-suppressor miRNA that targets Wnt-b-catenin signaling. Cancer Res; 74(24); 7560-72. Ó2014 AACR.

Integrated Analysis and MicroRNA Expression Profiling Identified Seven miRNAs Associated With Progression of Oral Squamous Cell Carcinoma

“…In order to identify the key miRNAs and their target genes in carcinogenesis of OSCC, and to explore the mechanism of carcinogenesis of OSCC, bioinformatics analysis was applied to select the key significantly up‐ and downregulated miRNAs from the eight currently available OSCC miRNA datasets (dataset 1, (Shiah et al, ); dataset 2 (Scapoli et al, ); dataset 3 (Soga et al, ); dataset 4 (Lu et al, ); dataset 5 (Kozaki et al, ); dataset 6 (Yu et al, ); dataset 7 (Momen‐Heravi et al, ); dataset 8 (Wong et al, )) (Table ). Furthermore, the potential target genes of the selected miRNAs were predicted, and of which function annotation and transcription factor (TF) analysis were performed as well (Fig.…”

Immunohistochemical staining with non-phospho β-catenin as a diagnostic and prognostic tool of COX-2 inhibitor therapy for patients with extra-peritoneal desmoid-type fibromatosis

“…We used colon carcinoma tissues for non-phospho β-catenin staining as a positive control, and non-aggressive fibrous tumors, fibroma, was also subjected to this staining. This non-phospho β-catenin antibody was also used for western blotting using oral squamous cell carcinoma in another previous study [25]. Nuclear and cytoplasmic positivity of β-catenin and non-phospho β-catenin were analyzed by two observers (S. H., T. S.) without the clinical information of cases, and classified into 4 groups according to definition of a previous report [21]; 0% for positively stained cells (negative; 0), 1% to 10% (weak; 1+), 11% to 50% (moderate; 2+) and 51% to 100% (strong; 3+) on 10 randomly selected high-power fields.…”

MicroRNA-17-5p regulated apoptosis-related protein expression and radiosensitivity in oral squamous cell carcinoma caused by betel nut chewing

“…Betel ( Areca catechu ) nut chewing is associated with the development of several types of oral cancers [8]. Betel nut chewing, which is widespread in Taiwan, is an independent risk factor for the development of squamous cell head and neck cancer.…”