Abstract 1952: Deregulated microRNA expression in the progression of salivary gland cancer.

Abstract

Abstract Salivary gland cancer constitutes one of the five main subsets of cancer in the head and neck region. Nonresectable malignant tumors demonstrate a low 20-year survival rate due to radioresistance and a high propensity for metastasis. The molecular mechanisms underlying pathogenesis of salivary cancer remains poorly elucidated, and thus necessitates further investigation. MicroRNAs (miRNA) are small noncoding RNAs that are predicted to regulate up to 30% of protein-encoding genes. Signature miRNA expression profiles have been identified in various malignancies, implicating miRNAs in the progression of human cancer. In order to better understand the role of miRNAs in the progression of salivary cancer, we profiled the miRNA expression levels of normal salivary tissue, benign salivary tumor, and salivary cancer. A total of 17 formalin-fixed paraffin-embedded salivary tissues, including 4 normal, 4 pleomorphic adenoma (PA), 3 squamous cell carcinoma (SCC), 3 mucoepidermoid carcinoma (ME) and 3 adenocarcinoma (AC), were collected and the endogenous expression of 95 miRNAs was analyzed by microarray. A large number of miRNAs were observed to be aberrantly expressed and generally down-regulated in salivary cancer and salivary tumor tissues with respect to normal salivary gland tissues. An unsupervised clustering and a student t-test were performed with a threshold p-value less than 0.05, resulting in the identification of 22 miRNAs differentially expressed at a statistically significant level. Eight candidate miRNAs were selected and further validated by RT-qPCR. The results suggest three miRNAs in SCC (miR-200a, let-7-family, and miR-192) and three miRNAs in AC (miR-107, miR-15b and miR-200a) to be highly involved in the carcinogenetic process of salivary cancers. Furthermore, the up-regulated expression pattern of miR-203 is indicative of a tumorigenetic function in salivary tumors. Interestingly, miR-200b was found to be consistently and significantly down regulated (p=0.01, 19.03 fold decrease) in the three types of salivary cancer under investigation. Recent studies have implicated miR-200b in EMT and invasion in cancer cells by directly targeting E-cadherin transcriptional repressors. The miRNAs identified in this study may serve as potential biomarkers and targets for future miRNA based therapy. Citation Format: Hao Zheng, Alan Kiang, Selena Z. Kuo, Elham Rahimy, Jessica Wang-Rodriguez, Weg M. Ongkeko. Deregulated microRNA expression in the progression of salivary gland cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1952. doi:10.1158/1538-7445.AM2013-1952