Abstract 5282: The role of T3-regulated microRNAs in human hepatoma cells.

Abstract

Abstract Thyroid hormone (T3)/thyroid hormone receptor (TR) signaling regulates cellular growth, development and differentiation, which play important roles in vivo. T3/TR signaling promotes invasion while suppressing proliferation of hepatoma cells. MicroRNAs (miRNA) are small, short, endogenously expressed non-coding RNAs that negatively regulate gene expression. Aberrant miRNA expression has been observed in various tumor types, including hepatocellular carcinoma. At present, it is unclear whether T3/TR signaling regulates miRNAs in hepatoma cells. In our laboratory, miRNA profiling analysis using the high-throughput stem-loop RT-qPCR method revealed upregulation of miR-21 by T3/TR. A native thyroid hormone response element was identified in the primary miR-21 promoter region using promoter and chromatin immunoprecipitation assays. Overexpression of miR-21 promoted hepatoma cell migration and invasion, similar to that observed with T3 stimulation in hepatoma cells. In addition, anti-miR-21-induced suppression of cell migration was rescued by T3. T-cell lymphoma invasion and metastasis 1 (Tiam1), involved in cell migration and invasion, was identified as a miR-21 target, and downregulated by T3. Tiam1 was upregulated upon knockdown of miR-21, and conversely, downregulated upon miR-21 overexpression. Further, knockdown of Tiam1 enhanced migration and invasion may through increase of vimentin and MMP2 expression in hepatoma cells. The correlation among T3/TR, miR-21 and Tiam1 was observed in vivo is similar with in vitro. These findings indicate that miR-21 is directly upregulated by T3. Moreover, T3-mediated enhancement of hepatoma cell migration and invasion may through miR-21-targeted downregulation of Tiam1. Citation Format: Ya-Hui Huang, Yang-Hsiang Lin, Ching-Ying Chen, Kwang-Huei Lin. The role of T3-regulated microRNAs in human hepatoma cells. [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 5282. doi:10.1158/1538-7445.AM2013-5282