Repression of microRNA-130b by thyroid hormone enhances cell motility.

Thyroid hormone (T3) and its receptor (TR) are involved in cell growth and cancer progression. Although deregulation of microRNA (miRNA) expression has been detected in many tumor types, the mechanisms underlying functional impairment and specific involvement of miRNAs in tumor metastasis remain unclear. In the current study, we aimed to elucidate the involvement of deregulated miRNA-130b (miR-130b) and its target genes mediated by T3/TR in cancer progression. Quantitative reverse transcription-PCR, luciferase and chromatin immunoprecipitation assays were performed to identify the miR-130b transcript and the mechanisms implicated in its regulation. The effects of miR-130b on hepatocellular carcinoma (HCC) invasion were further examined in vitro and in vivo. Clinical correlations among miR-130b, TRs and interferon regulatory factor 1 (IRF1) were examined in HCC samples using Spearman correlation analysis. Our experiments disclosed negative regulation of miR-130b expression by T3/TR. Overexpression of miR-130b led to marked inhibition of cell migration and invasion, which was mediated via suppression of IRF1. Cell migration ability was promoted by T3, but partially suppressed upon miR-130b overexpression. Furthermore, miR-130b suppressed expression of epithelial-mesenchymal transition (EMT)-related genes, matrix metalloproteinase-9, phosphorylated mammalian target of rapamycin (mTOR), p-ERK1/2, p-AKT and p-signal transducer and activator of transcription (STAT)-3. Notably, miR-130b was downregulated in hepatoma samples and its expression patterns were inversely correlated with those of TRα1 and IRF1. Our data collectively highlight a novel pathway interlinking T3/TR, miR-130b, IRF1, the EMT-related genes, p-mTOR, p-STAT3 and the p-AKT cascade, which regulates the motility and invasion of hepatoma cells.

Lin YH ，Wu MH ，Liao CJ ，Huang YH ，Chi HC ，Wu SM ，Chen CY ，Tseng YH ，Tsai CY ，Chung IH ，Tsai MM ，Chen CY ，Lin TP ，Yeh YH ，Chen WJ ，Lin KH ... -  《-》

miR-345 inhibits tumor metastasis and EMT by targeting IRF1-mediated mTOR/STAT3/AKT pathway in hepatocellular carcinoma.

Yu M ，Xue H ，Wang Y ，Shen Q ，Jiang Q ，Zhang X ，Li K ，Jia M ，Jia J ，Xu J ，Tian Y ... -  《-》

Thyroid hormone receptor represses miR-17 expression to enhance tumor metastasis in human hepatoma cells.

Lin YH ，Liao CJ ，Huang YH ，Wu MH ，Chi HC ，Wu SM ，Chen CY ，Tseng YH ，Tsai CY ，Chung IH ，Wu TI ，Tsai MM ，Lin CD ，Lin KH ... -  《-》

Thyroid hormone regulation of miR-21 enhances migration and invasion of hepatoma.

Thyroid hormone (T(3)) signaling through the thyroid hormone receptor (TRα1) regulates hepatoma cell growth and pathophysiology, but the underlying mechanisms are unclear at present. Here, we have shown that the oncomir microRNA-21 (miR-21) is activated by T(3) through a native T(3) response element in the primary miR-21 promoter. Overexpression of miR-21 promoted hepatoma cell migration and invasion, similar to that observed with T(3) stimulation in hepatoma cells. In addition, anti-miR-21-induced suppression of cell migration was rescued by T(3). The Rac-controlled regulator of invasion and metastasis, T-cell lymphoma invasion and metastasis 1 (TIAM1), was identified as a miR-21 target additionally downregulated by T(3). Attenuation and overexpression of miR-21 induced upregulation and downregulation of TIAM1, respectively. TIAM1 attenuation, in turn, enhanced migration and invasion via the upregulation of β-catenin, vimentin, and matrix metalloproteinase-2 in hepatoma cells. Notably, correlations between TRα1, miR-21, and TIAM1 expression patterns in animal models paralleled those observed in vitro. In the clinic, we observed a positive correlation (P = 0.005) between the tumor/nontumor ratios of TRα1 and miR-21 expression, whereas a negative correlation (P = 0.019) was seen between miR-21 and TIAM1 expression in patients with hepatoma. Our findings collectively indicate that miR-21 stimulation by T(3) and subsequent TIAM1 suppression promotes hepatoma cell migration and invasion.

Huang YH ，Lin YH ，Chi HC ，Liao CH ，Liao CJ ，Wu SM ，Chen CY ，Tseng YH ，Tsai CY ，Lin SY ，Hung YT ，Wang CJ ，Lin CD ，Lin KH ... -  《-》

[The expression and clinopathological significance of miR-130b in human hepatocellular carcinoma].

Xu Q ，Cai W ，Zhang M ，Liu Q ，Liu X ... -  《-》