BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
권호 표지
DOI QR코드

DOI QR Code

TCP10L negatively regulates alpha-fetoprotein expression in hepatocellular carcinoma

  • Shen, Suqin (The State Key Laboratory of Genetic Engineering, Zhongshan Hospital and School of Life Science, Fudan University) ;
  • Feng, Huan (The State Key Laboratory of Genetic Engineering, Zhongshan Hospital and School of Life Science, Fudan University) ;
  • Liu, Longjiang (The State Key Laboratory of Genetic Engineering, Zhongshan Hospital and School of Life Science, Fudan University) ;
  • Su, Wei (The State Key Laboratory of Genetic Engineering, Zhongshan Hospital and School of Life Science, Fudan University) ;
  • Yu, Long (The State Key Laboratory of Genetic Engineering, Zhongshan Hospital and School of Life Science, Fudan University) ;
  • Wu, Jiaxue (The State Key Laboratory of Genetic Engineering, Zhongshan Hospital and School of Life Science, Fudan University)
  • 투고 : 2020.01.10
  • 심사 : 2020.02.25
  • 발행 : 2020.08.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Alpha-fetoprotein (AFP) is one of the most commonly used and reliable biomarkers for Hepatocellular carcinoma（HCC). However, the underlying mechanism of AFP expression in HCC is poorly understood. In this study, we found that TCP10L, a gene specifically expressed in the liver, is down-regulated in HCC and that its expression inversely correlates with AFP expression. Moreover, overexpression of TCP10L suppresses AFP expression whereas knockdown of TCP10L increases AFP expression, suggesting that TCP10L might be a negative regulator of AFP. We found that TCP10L is associated with the AFP promoter and inhibits AFP promoter-driven transcriptional activity. Taken together, these results indicate that TCP10L negatively regulates AFP expression in HCC and that it could be a potential prognostic marker and therapeutic target for HCC.

키워드

참고문헌

  1. Villanueva A (2019) Hepatocellular carcinoma. N Engl J Med 380, 1450-1462 https://doi.org/10.1056/NEJMra1713263
  2. Hanahan D and Weinberg RA (2011). Hallmarks of Cancer: The Next Generation. Cell 144, 646-674 https://doi.org/10.1016/j.cell.2011.02.013
  3. Cidon EU (2017) Systemic treatment of hepatocellular carcinoma: Past, present and future. World J Hepatol 9, 797-807 https://doi.org/10.4254/wjh.v9.i18.797
  4. Chaffer CL and Weinberg RA (2011) A Perspective on Cancer Cell Metastasis. Science 331, 1559-1564 https://doi.org/10.1126/science.1203543
  5. Tilghman SM (1985) The structure and regulation of the alpha-fetoprotein and albumin genes. Oxf Surv Eukaryot Genes 2, 160-206
  6. Chen H, Egan JO and Chiu JF (1997) Regulation and activities of alpha-fetoprotein. Crit Rev Eukaryot Gene Expr 7, 11-41 https://doi.org/10.1615/CritRevEukarGeneExpr.v7.i1-2.20
  7. Feuerman MH, Godbout R, Ingram RS and Tilghman SM (1989) Tissue-Specific Transcription of the Mouse Alpha-Fetoprotein Gene Promoter Is Dependent on Hnf-1. Mol Cell Biol 9, 4204-4212 https://doi.org/10.1128/MCB.9.10.4204
  8. Boisjoyeux B and Danan JL (1994) Members of the CAAT/Enhancer-Binding Protein, Hepatocyte Nuclear Factor-I and Nuclear Factor-I Families Can Differentially Modulate the Activities of the Rat Alpha-Fetoprotein Promoter and Enhancer. Biochem J 301, 49-55 https://doi.org/10.1042/bj3010049
  9. Xie Z, Zhang H, Tsai W et al (2008) Zinc finger protein ZBTB20 is a key repressor of alpha-fetoprotein gene transcription in liver. Proc Natl Acad Sci U S A 105, 10859-10864 https://doi.org/10.1073/pnas.0800647105
  10. Zhang H, Cao DM, Zhou LT et al (2015) ZBTB20 is a sequence-specific transcriptional repressor of alpha-fetoprotein gene. Sci Rep 5,11979 https://doi.org/10.1038/srep11979
  11. Shen H, Luan F, Liu H et al (2008) ZHX2 is a repressor of alpha-fetoprotein expression in human hepatoma cell lines. J Cell Mol Med 12, 2772-2780 https://doi.org/10.1111/j.1582-4934.2008.00233.x
  12. Lee KC, Crowe AJ and Barton MC (1999) p53-mediated repression of alpha-fetoprotein gene expression by specific DNA binding. Mol Cell Biol 19, 1279-1288 https://doi.org/10.1128/MCB.19.2.1279
  13. Nguyen TT, Cho K, Stratton SA and Barton MC (2005) Transcription factor interactions and chromatin modifications associated with p53-mediated, developmental repression of the alpha-fetoprotein gene. Mol Cell Biol 25, 2147-2157 https://doi.org/10.1128/MCB.25.6.2147-2157.2005
  14. Chen Z, Yu L, Wu H et al (2003) Identification of a novel liver-specific expressed gene, TCP10L, encoding a human leucine zipper protein with transcription inhibition activity. J Hum Genet 48, 556-563 https://doi.org/10.1007/s10038-003-0075-6
  15. Zhong Z, Qiu J, Chen X et al (2008) Identification of TCP10L as primate-specific gene derived via segmental duplication and homodimerization of TCP10L through the leucine zipper motif. Mol Biol Rep 35, 171-178 https://doi.org/10.1007/s11033-007-9067-5
  16. Jiang DJ, Yu HX, Hexige SY et al (2004) Human liver specific transcriptional factor TCP10L binds to MAD4. J Biochem Mol Biol 37, 402-407
  17. Zhong ZM, Qiu JP, Chen XY et al (2008) Identification of TCP10L as primate-specific gene derived via segmental duplication and homodimerization of TCP10L through the leucine zipper motif. Mol Biol Rep 35, 171-178 https://doi.org/10.1007/s11033-007-9067-5
  18. Yu HX, Jiang DJ, Guo ZK et al (2005) TCP10L is expressed specifically in spermatogenic cells and binds to death associated protein kinase-3. Int J Androl 28, 163-170 https://doi.org/10.1111/j.1365-2605.2005.00522.x
  19. Shen SQ, Zuo J, Feng H et al (2016) TCP10L synergizes with MAD1 in transcriptional suppression and cell cycle arrest through mutual interaction. BMB Rep 49, 325-330 https://doi.org/10.5483/BMBRep.2016.49.6.248
  20. Zuo J, Cai H, Wu Y et al (2014) TCP10L acts as a tumor suppressor by inhibiting cell proliferation in hepatocellular carcinoma. Biochem Biophys Res Commun 446, 61-67 https://doi.org/10.1016/j.bbrc.2014.02.049
  21. Chen Z, Yu L, Wu H et al (2003) Identification of a novel liver-specific expressed gene, TCP10L, encoding a human leucine zipper protein with transcription inhibition activity. J Hum Genet 48, 556-563 https://doi.org/10.1007/s10038-003-0075-6
  22. Johnson AD (1995) The Price of Repression. Cell 81, 655-658 https://doi.org/10.1016/0092-8674(95)90524-3
  23. Gray S and Levine M (1996) Transcriptional repression in development. Curr Opin Cell Biol 8, 358-364 https://doi.org/10.1016/S0955-0674(96)80010-X
  24. Biamonti G and Riva S (1994) New insights into the auxiliary domains of eukaryotic RNA binding proteins. FEBS Lett 340, 1-8 https://doi.org/10.1016/0014-5793(94)80162-2
  25. Leng X, Cooney AJ, Tsai SY and Tsai MJ (1996) Molecular mechanisms of COUP-TF-mediated transcriptional repression: Evidence for transrepression and active repression. Mol Cell Biol 16, 2332-2340 https://doi.org/10.1128/MCB.16.5.2332
  26. Peyton DK, Huang MC, Giglia MA, Hughes NK and Spear BT (2000) The alpha-fetoprotein promoter is the target of Afr1-mediated postnatal repression. Genomics 63, 173-180 https://doi.org/10.1006/geno.1999.6073
  27. Jin DK, Vacher J and Feuerman MH (1998) Alpha-Fetoprotein gene sequences mediating Afr2 regulation during liver regeneration. Proc Natl Acad Sci U S A 95, 8767-8772 https://doi.org/10.1073/pnas.95.15.8767
  28. Li MS, Li PF, He SP, Du GG and Li G (2000) The promoting molecular mechanism of alpha-fetoprotein on the growth of human hepatoma Bel7402 cell line. World J Gastroenterol 8, 469-475 https://doi.org/10.3748/wjg.v8.i3.469
  29. Li MS, Li PF, Chen Q et al (2004) Alpha-fetoprotein stimulated the expression of some oncogenes in human hepatocellular carcinoma Bel 7402 cells. World J Gastroenterol 10, 819-824 https://doi.org/10.3748/wjg.v10.i6.819
  30. Nakao K and Ichikawa T (2013) Recent topics on alphafetoprotein. Hepatol Res 43, 820-825 https://doi.org/10.1111/hepr.12052