Abstract 4143: microRNA-874 as a tumor suppressor in maxillary sinus squamous cell carcinoma based on microRNA expression signature

Abstract

Abstract (BACKGROUND) Maxillary sinus squamous cell carcinoma (MSSCC) comprises 2-3% of all cancers of head and neck tumor and the annual incidence rate is 0.5-1.0 per 100,000 populations. After introduction of multimodality treatment comprising radiation therapy along with concomitant intra-arterial chemotherapy, rates of local control was improved. However the prognosis of advanced MSSCC is still worse. The 5-years survival rate of T4 tumors is 50% around. Local recurrence is the most common cause of treatment failure and death. Greater understanding of the molecular oncogenic network in MSSCC could help improve diagnosis, therapy, and prevention of the disease. No studies have been carried out for the purpose of identifying specific microRNA (miRNA) alterations in MSSCC. In this study, we focused on the functional siginificance of the most downregulated miRNA in MSSCC on the basis of miRNA expression signature. (METHODS) We used PCR-based methods to investigate the downregulated miRNAs in clinical specimens of MSSCC. Genome-wide gene expression analysis was performed to identify the molecular networks of microRNA-874 (miR-874) by microarray technique. Cell proliferation and invasion assays were performed to investigate the functional significance of miR-874 and its target genes in MSSCC cell lines. (RESULTS) Our miRNA signature identified that 23 miRNAs were significantly reduced in cancer cells. We focused on miR-874 as the most downregulated novel miRNA in our analysis. Ectopic miR-874 overexpression showed potential tumour suppressive functions such as inhibition of cancer cell proliferation and invasion. A molecular target search of miR-874 revealed that protein phosphatase 1, catalytic subunit, alpha isozyme (PPP1CA), proteasomal ATPase-associated factor 1 (PAAF1) and trans-golgi network protein 2 (TGOLN2) were regulated by miR-874. Overexpression of these genes was observed in MSSCC clinical specimens and each gene expression was inversely correlated with miR-874 expression. Moreover, silencing of the PPP1CA gene significantly inhibited cancer cell proliferation and invasion. (CONCLUSION) The downregulation of miR-874 was a frequent event in MSSCC, which suggests that miR-874 functions as a tumour suppressive miRNA, directly regulating PPP1CA that has a potential role of an oncogene. The identification of novel miR-874-regulated cancer network could provide new insights into potential molecular mechanisms of MSSCC oncogenesis. 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 4143. doi:1538-7445.AM2012-4143