Identification of oral carcinoma miRNA involved in Wnt/b-catenin signaling

ABSTRACT: MicroRNAs (miRNAs) participate in many biological processes and have emerged as key players in carcinogenesis. In order to identify changes in miRNAs specific for betelquid-associated oral squamous cell carcinoma (OSCC), we investigated the expression profiles of 858 miRNAs in a panel of 40 pairs of OSCC specimens and their matched non-tumorous epithelial counterparts. Eighty-four miRNAs were differentially expressed in the OSCC specimens compared to the matched tissue. Among these miRNAs, 19 downregulated miRNAs located in the chromosome 14q32.2 miRNA cluster region were analyzed. This miRNA cluster resides within a parentally imprinted region known to be important in development and growth. The re-expression of miR-329 and miR-410from this cluster significantly reduced OSCC cell proliferation and invasion and downregulated Wnt-7b, an activator of the Wnt/b-catenin pathway. Furthermore, the expression of those 2 miRNAs was restored by 5-aza-2′-deoxycytidine treatment and the expression levels of the 2 miRNAs were inversely correlated with the hypermethylation of the Meg-3 promoter in OSCC cells. Specifically, arecoline, a major betel nut alkaloid, reduces miR-329 and miR-410 expression. Our results thus provide a novel molecular insight into how betel quid may contribute to oral carcinogenesis through the epigenetic silencing of tumor suppressor miRNAs targeting the Wnt/b-catenin signaling pathway. Total RNA was obtained from 40 pairs of OSCC patients with tumor specimens and their adjacent non-tumorous epithelia.

ORGANISM(S): Homo sapiens

SUBMITTER: Shine-Gwo Shiah 

PROVIDER: E-GEOD-45238 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress