Abstract 3098: MiRNA-145 is a master regulator of the hallmarks of thyroid cancer.

Abstract

Abstract microRNA-145 (miR-145) in an important member of the family of microRNAs which are downregulated in several types of tumors. However, miR-145 expression and function in thyroid cancer and in cellular differentiation is unknown. In our study, we performed miRNA profiling in normal, benign and malignant thyroid cancers including undifferentiated tumors with validation of differentially expressed miRNAs by quantitative RT PCR. We found significant downregulation of miR-145 in differentiated and undifferentiated thyroid cancer. We performed functional studies in thyroid cancer cell lines and found that miR-145 decreases cell proliferation, induces cell cycle arrest, decreases cell invasion and targets the PI3K/Akt pathway, one of the most commonly activated pathways in thyroid cancer and which is associated with epithelial-mesenchymal transition (EMT). Overexpression of miR-145 in cell lines also decreased the expression of EMT markers vimentin and N-cadherin. Furthermore, inhibition of miR-145 in normal primary thyroid cultured cells decreased NIS and PAX8 expression, key regulators of thyroid cell differentiation. miRNA-145 expression in tumor tissue was inversely correlated with VEGF serum levels in the same patients and overexpression of miR-145 in vitro decreased angiogenesis and VEGF secretion. MiRNA-145 has important regulatory effects on the hallmarks of thyroid cancer cells and thus may be involved in thyroid cancer progression. Citation Format: Myriem Boufraqech, Lisa Zhang, Meenu Jain, Neelam Gulati, Naris Nilubol, Mio Kitano, Yin Xiong, Electron Kebebew. MiRNA-145 is a master regulator of the hallmarks of thyroid 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 3098. doi:10.1158/1538-7445.AM2013-3098