| Summary: | 碩士 === 長庚大學 === 基礎醫學研究所 === 95 === Thyroid hormone (T3) regulates metabolism, growth, development, and differentiation. These activities are mediated by the nuclear thyroid hormone receptor (TRs). Previously, cDNA microarrays were performed; methionine adenosyltransferase 1A (MAT1A) was up-regulated by T3/TR. Methionine adenosyltransferase is an essential cellular enzyme which catalyses the formation of S-adenosylmethionine (SAM), the principal methyl donor and the precursor of polyamines. Here we investigated the biological significance of MAT1A regulation by T3 in HepG2 cell. MAT1A mRNA and protein expression were increased by T3 in HepG2-TR cells that over-expressing TR. Methionine adenosyltransferase activity was elevated after T3 treatment. The protein synthesis inhibitor, cycloheximide, inhibited the induction of MAT1A by T3, indicating that this regulation was indirect. MATⅠ/Ⅲ was silenced in hepatocellular carcinoma. Knock-down of MATIA expression raised cell migration and the activities of pro-MMP2, pro-MMP9 and MMP-9 in HepG2 cells. The mRNA expression of metastasis related genes (E-cadherin and β-catenin) were changed in MAT1A-knockdown stable clones. Together, this study demonstrates that MAT1A gene expression is indirectly up-regulated by T3. T3 may regulate cellular metabolism through up-regulated MAT1A. Furthermore, the regulation of T3/TR may play a suppressor role in hepatocarcinogenesis.
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