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Thyroid hormone receptor-mediated regulation of the methionine adenosyltransferase 1 gene is associated with cell invasion in hepatoma cell lines

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Abstract

The thyroid hormone T3 regulates differentiation, growth, and development. We demonstrated that methionine adenosyltransferase 1A (MAT1A) was positively regulated by T3 identified by cDNA microarray previously. The expression of the MAT1A was upregulated by T3 in hepatoma cell lines overexpressing thyroid hormone receptors (TRs). Additionally, these findings indicate that MAT1A may be regulated by CCAAT/enhancer binding protein (C/EBP). The critical role of the C/EBP binding sites was confirmed by the reporter or chromatin immuno-precipitation (ChIP) assay. In addition, C/EBP was upregulated in hepatoma cells after T3 treatment and ectopic expression of MAT1A inhibited cell migration and invasion in J7 hepatoma cells. Conversely, knockdown of MAT1A expression increased cell migration. Together, these findings suggest that the expression of the MAT1A gene is mediated by C/EBP and is indirectly upregulated by T3. Finally, TR was downregulated in a small subset of hepatocellular carcinoma cells concomitantly reduced the expression of C/EBPα and MAT1A.

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References

  1. Aranda A, Pascual A (2001) Nuclear hormone receptors and gene expression. Physiol Rev 81:1269–1304

    CAS  PubMed  Google Scholar 

  2. Dayan CM, Panicker V (2009) Novel insights into thyroid hormones from the study of common genetic variation. Nat Rev Endocrinol 5:211–218

    Article  CAS  PubMed  Google Scholar 

  3. Oetting A, Yen PM (2007) New insights into thyroid hormone action. Best Pract Res Clin Endocrinol Metab 21:193–208

    Article  CAS  PubMed  Google Scholar 

  4. Puzianowska-Kuznicka M, Pietrzak M, Turowska O, Nauman A (2006) Thyroid hormones and their receptors in the regulation of cell proliferation. Acta Biochim Pol 53:641–650

    CAS  PubMed  Google Scholar 

  5. Huang YH, Tsai MM, Lin KH (2008) Thyroid hormone dependent regulation of target genes and their physiological significance. Chang Gung Med J 31:325–334

    PubMed  Google Scholar 

  6. Hulbert AJ (2000) Thyroid hormones and their effects: a new perspective. Biol Rev Camb Philos Soc 75:519–631

    Article  CAS  PubMed  Google Scholar 

  7. Cheng SY (2000) Multiple mechanisms for regulation of the transcriptional activity of thyroid hormone receptors. Rev Endocr Metab Disord 1:9–18

    Article  CAS  PubMed  Google Scholar 

  8. Yen PM (2001) Physiological and molecular basis of thyroid hormone action. Physiol Rev 81:1097–1142

    CAS  PubMed  Google Scholar 

  9. Ding XF, Anderson CM, Ma H, Hong H, Uht RM, Kushner PJ, Stallcup MR (1998) Nuclear receptor-binding sites of coactivators glucocorticoid receptor interacting protein 1 (GRIP1) and steroid receptor coactivator 1 (SRC-1): multiple motifs with different binding specificities. Mol Endocrinol 12:302–313

    Article  CAS  PubMed  Google Scholar 

  10. Li J, Wang J, Nawaz Z, Liu JM, Qin J, Wong J (2000) Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3. EMBO J 19:4342–4350

    Article  CAS  PubMed  Google Scholar 

  11. Chamba A, Neuberger J, Strain A, Hopkins J, Sheppard MC, Franklyn JA (1996) Expression and function of thyroid hormone receptor variants in normal and chronically diseased human liver. J Clin Endocrinol Metab 81:360–367

    Article  CAS  PubMed  Google Scholar 

  12. Ara AI, Xia M, Ramani K, Mato JM, Lu SC (2008) S-adenosylmethionine inhibits lipopolysaccharide-induced gene expression via modulation of histone methylation. Hepatology 47:1655–1666

    Article  CAS  PubMed  Google Scholar 

  13. Lu SC, Mato JM (2008) S-Adenosylmethionine in cell growth, apoptosis and liver cancer. J Gastroenterol Hepatol 23(Suppl 1):S73–S77

    Article  CAS  PubMed  Google Scholar 

  14. Mato JM, Martinez-Chantar ML, Lu SC (2008) Methionine metabolism and liver disease. Annu Rev Nutr 28:273–293

    Article  CAS  PubMed  Google Scholar 

  15. Shih CH, Chen SL, Yen CC, Huang YH, Chen CD, Lee YS, Lin KH (2004) Thyroid hormone receptor-dependent transcriptional regulation of fibrinogen and coagulation proteins. Endocrinology 145:2804–2814

    Article  CAS  PubMed  Google Scholar 

  16. Chen RN, Huang YH, Lin YC, Yeh CT, Liang Y, Chen SL, Lin KH (2008) Thyroid hormone promotes cell invasion through activation of furin expression in human hepatoma cell lines. Endocrinology 149:3817–3831

    Article  CAS  PubMed  Google Scholar 

  17. Chen RN, Huang YH, Yeh CT, Liao CH, Lin KH (2008) Thyroid hormone receptors suppress pituitary tumor transforming gene 1 activity in hepatoma. Cancer Res 68:1697–1706

    Article  CAS  PubMed  Google Scholar 

  18. Samuels HH, Stanley F, Casanova J (1979) Depletion of l-3, 5, 3′-triiodothyronine and l-thyroxine in euthyroid calf serum for use in cell culture studies of the action of thyroid hormone. Endocrinology 105:80–85

    Article  CAS  PubMed  Google Scholar 

  19. Tai PJ, Huang YH, Shih CH, Chen RN, Chen CD, Chen WJ, Wang CS, Lin KH (2007) Direct regulation of androgen receptor-associated protein 70 by thyroid hormone and its receptors. Endocrinology 148:3485–3495

    Article  CAS  PubMed  Google Scholar 

  20. Zeng Z, Huang ZZ, Chen C, Yang H, Mao Z, Lu SC (2000) Cloning and functional characterization of the 5′-flanking region of human methionine adenosyltransferase 1A gene. Biochem J 346(Pt 2):475-482

    Google Scholar 

  21. Huang YH, Lee CY, Tai PJ, Yen CC, Liao CY, Chen WJ, Liao CJ, Cheng WL, Chen RN, Wu SM, Wang CS, Lin KH (2006) Indirect regulation of human dehydroepiandrosterone sulfotransferase family 1A member 2 by thyroid hormones. Endocrinology 147:2481–2489

    Article  CAS  PubMed  Google Scholar 

  22. Zhu QS, Qian B, Levy D (2004) Regulation of human microsomal epoxide hydrolase gene (EPHX1) expression by the transcription factor GATA-4. Biochim Biophys Acta 1676:251–260

    CAS  PubMed  Google Scholar 

  23. Repesh LA (1989) A new in vitro assay for quantitating tumor cell invasion. Invasion Metastasis 9:192–208

    CAS  PubMed  Google Scholar 

  24. Sternlicht MD, Werb Z (2001) How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol 17:463–516

    Article  CAS  PubMed  Google Scholar 

  25. Yen CC, Huang YH, Liao CY, Liao CJ, Cheng WL, Chen WJ, Lin KH (2006) Mediation of the inhibitory effect of thyroid hormone on proliferation of hepatoma cells by transforming growth factor-beta. J Mol Endocrinol 36:9–21

    Article  CAS  PubMed  Google Scholar 

  26. Tseng HH, Hwang YH, Yeh KT, Chang JG, Chen YL, Yu HS (2009) Reduced expression of C/EBP alpha protein in hepatocellular carcinoma is associated with advanced tumor stage and shortened patient survival. J Cancer Res Clin Oncol 135:241–247

    Article  CAS  PubMed  Google Scholar 

  27. Rountree CB, Senadheera S, Mato JM, Crooks GM, Lu SC (2008) Expansion of liver cancer stem cells during aging in methionine adenosyltransferase 1A-deficient mice. Hepatology 47:1288–1297

    Article  CAS  PubMed  Google Scholar 

  28. Qin L, Liu Z, Chen H, Xu J (2009) The steroid receptor coactivator-1 regulates twist expression and promotes breast cancer metastasis. Cancer Res 69:3819–3827

    Article  CAS  PubMed  Google Scholar 

  29. Li S, Jiao J, Lu Z, Zhang M (2009) An essential role for N-cadherin and beta-catenin for progression in tongue squamous cell carcinoma and their effect on invasion and metastasis of Tca8113 tongue cancer cells. Oncol Rep 21:1223–1233

    CAS  PubMed  Google Scholar 

  30. Ikeda R, Nishida T, Watanabe F, Shimizu-Saito K, Asahina K, Horikawa S, Teraoka H (2008) Involvement of CCAAT/enhancer binding protein-beta (C/EBPbeta) in epigenetic regulation of mouse methionine adenosyltransferase 1A gene expression. Int J Biochem Cell Biol 40:1956–1969

    Article  CAS  PubMed  Google Scholar 

  31. Frago LM, Paneda C, Fabregat I, Varela-Nieto I (2001) Short-chain ceramide regulates hepatic methionine adenosyltransferase expression. J Hepatol 34:192–201

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from Chang-Gung University, Taoyuan, Taiwan (CMRPD 34013, NMRP 140511) and from the National Science Council of the Republic of China (NSC 94-2320-B-182-052).

Conflict of interest statement

The authors declare that there is no conflict of interest that would prejudice the impartiality of this scientific work.

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Authors and Affiliations

  1. Department of Biochemistry, School of Medicine, Chang-Gung University, 259 Wen-hwa 1 Road, Taoyuan, 333, Taiwan, ROC

    Sheng-Ming Wu, Yi-Hsin Lu, Ling-Fang Chien, Ming-Ming Tsai, Chen-Hsin Liao, Chia-Jung Liao, Wan-Li Cheng & Kwang-Huei Lin

  2. Medical Research Center, Chang-Gung Memorial Hospital, Taoyuan, Taiwan, ROC

    Ya-Hui Huang

  3. Department of Medicine, College of Medicine, Chang-Gung University, Taoyuan, 333, Taiwan, ROC

    Chau-Ting Yeh

  4. Liver Research Unit, Chang-Gung Medical Center, Taipei, Taiwan, ROC

    Chau-Ting Yeh

  5. Department of Nursing, Chang-Gung Institute of Technology, Taoyuan, 333, Taiwan, ROC

    Ming-Ming Tsai

  6. First Cardiovascular Division, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC

    Wei-Jan Chen

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  1. Sheng-Ming Wu
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Correspondence to Kwang-Huei Lin.

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Wu, SM., Huang, YH., Lu, YH. et al. Thyroid hormone receptor-mediated regulation of the methionine adenosyltransferase 1 gene is associated with cell invasion in hepatoma cell lines. Cell. Mol. Life Sci. 67, 1831–1843 (2010). https://doi.org/10.1007/s00018-010-0281-2

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  • DOI: https://doi.org/10.1007/s00018-010-0281-2

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