Abstract 1445: Thyroid hormone receptor represses microRNA-130b to enhance cell metastasis

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Thyroid hormone (T3) and its receptor (TR) are involved in cell growth and cancer progression. Although deregulation of miRNA expression has been detected in many tumor types, the mechanisms underlying functional impairment and specific involvement of miRNA in tumor metastasis remain unclear. We proposed that deregulation of specific miRNAs and target gene expressions mediated by T3/TR constitute critical steps of cancer progression. In the current study, we demonstrated that T3/TR negatively regulates microRNA-130b (miR-130b) expression, both in vitro and in vivo. Overexpression of miR-130b markedly inhibited cell migration and invasion in vitro and in vivo, which was mediated via suppression of interferon regulatory factor 1 (IRF1). Cell migration ability was promoted by T3, but partially suppressed upon miR-130b overexpression. Furthermore, miR-130b suppressed the expression of epithelial-mesenchymal transition (EMT)-related genes, matrix metalloproteinase (MMP)-9, p-AKT and p-signal transducer and activator of transcription (STAT)-3. Notably, miR-130b was downregulated in hepatoma samples and inversely correlated with TR and IRF1. Our data collectively highlight a novel pathway interlinking T3/TR, miR-130b, EMT-related genes, MMP9, p-AKT and p-STAT3 cascade that regulates the motility and invasion of hepatoma cells. Thus, miR-130b activation may be a useful strategy for cancer treatment in metastatic HCC. Citation Format: Yang Hsiang Lin, Meng-Han Wu, Yung-Hsin Yeh, Angel Chao, Kwang-Huei Lin. Thyroid hormone receptor represses microRNA-130b to enhance cell metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1445. doi:10.1158/1538-7445.AM2014-1445