Abstract 3164: MiR-134 expression is oncogenic for oral cancer

Abstract

Abstract Introduction Oral squamous cell carcinoma (OSCC) is one of the most prevalent malignant diseases around the worldwide. Understanding the pathogenetic basis of these tumors will bestow profound benefits in resolution of this disease, to validate individualized therapy and reduction in medical resources consumption. MicroRNA (miRNA) is a short, non-coding RNA that regulates gene expression by controlling mRNA translation. Which can affect biological and pathological processes. Dysregulation of miRNA function might lead to human disease including human cancers. Upregulation of miR-134 in OSCC was observed in a our previous study. However, the clinical implications and functions of miR-134 in oral tumorigenesis remain unclear. Methods Quantitative RT-PCR was used to analyze the miR-134 expression in OSCC tissue pairs. The oncogenic phenotypes including proliferation, migration and anchorage-independent colony formation were assayed in cells with miR-134 expression or miR-134 blockage. The xenografic tumorigenecity was assayed on nude mice model. TargetScan predicted WW domain-containing oxidoreductase (WWOX) a tumor suppressor gene to be putative targets of miR-134. To test the targeting activity of miR-134, antisense sequences complementary to miR-134 sequences and the 3β untranslatedregion (UTR) of WWOX containing predictive miR-134 target sites were cloned into the pCMV-LacZ plasmid at the 3α-end of the lacZ coding sequence; these reporter plasmids were designated miR-134-asR and pCMV-LacZ-WWOX3αUTR, respectively. Results miR-134 was found to be markedly upregulated in cancerous tissues than in non-cancerous matched tissues in OSCC tissue pairs. Higher miR-134 was associated with the more advanced tumor size and vascular invasion. Transfection of miR-134 precursor transiently upregulated miR-134 expression in OSCC cells. It increased oncogenic potential of OSCC cells. Conversely, the in vitro oncogenic potential of OSCC cells was attenuated after blocking of miR-134 expression. Stable SAS OSCC cell subclone with ectopic miR-134 expression was established by lentiviral delivery. Ectopic miR-134 expression increased the tumorigenicity of SAS subclone. Downregulation of WWOX mRNA expression and protein expression was found in SAS-miR-134 cells compared with controls. Conversely, upregulation of WWOX mRNA expression and protein on miR-134 LNA treatment relative to controls was found. Conclusion This identified for the first time that miR-134 is oncogenic to oral epithelium and its expression level could be validated as a diagnostic marker of OSCC. Our findings suggest that miR-134 contributes to the development of OSCC by targeting WWOX. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3164. doi:1538-7445.AM2012-3164