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GATA4 Forms a Positive Feedback Loop with CDX2 to Transactivate MUC2 in Bile Acids-Induced Gastric Intestinal Metaplasia

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Background/Aims: Gastric intestinal metaplasia (GIM), a common precancerous lesion of gastric cancer, can be caused by bile acid reflux. GATA binding protein 4 (GATA4) is an intestinal transcription factor involved in the progression of gastric cancer. However, the expression and regulation of GATA4 in GIM has not been clarified. Methods: The expression of GATA4 in bile acid-induced cell models and human specimens was examined. The transcriptional regulation of GATA4 was investigated by chromatin immunoprecipitation and luciferase reporter gene analysis. An animal model of duodenogastric reflux was used to confirm the regulation of GATA4 and its target genes by bile acids. Results: GATA4 expression was elevated in bile acid-induced GIM and human specimens. GATA4 bound to the promoter of mucin 2 (MUC2) and stimulate its transcription. GATA4 and MUC2 expression was positively correlated in GIM tissues. Nuclear transcription factor-κB activation was required for the upregulation of GATA4 and MUC2 in bile acid-induced GIM cell models. GATA4 and caudal-related homeobox 2 (CDX2) reciprocally transactivated each other to drive the transcription of MUC2. In chenodeoxycholic acid-treated mice, MUC2, CDX2, GATA4, p50, and p65 expression levels were increased in the gastric mucosa. Conclusions: GATA4 is upregulated and can form a positive feedback loop with CDX2 to transactivate MUC2 in GIM. NF-κB signaling is involved in the upregulation of GATA4 by chenodeoxycholic acid.

Abstract

Background/Aims: Gastric intestinal metaplasia (GIM), a common precancerous lesion of gastric cancer, can be caused by bile acid reflux. GATA binding protein 4 (GATA4) is an intestinal transcription factor involved in the progression of gastric cancer. However, the expression and regulation of GATA4 in GIM has not been clarified. Methods: The expression of GATA4 in bile acid-induced cell models and human specimens was examined. The transcriptional regulation of GATA4 was investigated by chromatin immunoprecipitation and luciferase reporter gene analysis. An animal model of duodenogastric reflux was used to confirm the regulation of GATA4 and its target genes by bile acids. Results: GATA4 expression was elevated in bile acid-induced GIM and human specimens. GATA4 bound to the promoter of mucin 2 (MUC2) and stimulate its transcription. GATA4 and MUC2 expression was positively correlated in GIM tissues. Nuclear transcription factor-κB activation was required for the upregulation of GATA4 and MUC2 in bile acid-induced GIM cell models. GATA4 and caudal-related homeobox 2 (CDX2) reciprocally transactivated each other to drive the transcription of MUC2. In chenodeoxycholic acid-treated mice, MUC2, CDX2, GATA4, p50, and p65 expression levels were increased in the gastric mucosa. Conclusions: GATA4 is upregulated and can form a positive feedback loop with CDX2 to transactivate MUC2 in GIM. NF-κB signaling is involved in the upregulation of GATA4 by chenodeoxycholic acid.

참고문헌 (46)

  1. Sung H, "Global cancer statistics 2020 : GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries", CA Cancer J Clin, 71, pp.209~249 (2021)
  2. Sumiyama K, "Past and current trends in endoscopic diagnosis for early stage gastric cancer in Japan", Gastric Cancer, 20(Suppl 1), pp.20~27 (2017)
  3. Katai H, "Five-year survival analysis of surgically resected gastric cancer cases in Japan : a retrospective analysis of more than 100, 000 patients from the nationwide registry of the Japanese Gastric Cancer Association(2001-2007)", Gastric Cancer, 21, pp.144~154 (2018)
  4. Correa P, "Human gastric carcinogenesis : a multistep and multifactorial process : first American Cancer Society Award Lecture on cancer epidemiology and prevention", Cancer Res, 52, pp.6735~6740 (1992)
  5. de Vries AC, "Gastric cancer risk in patients with premalignant gastric lesions : a nationwide cohort study in the Netherlands", Gastroenterology, 134, pp.945~952 (2008)
  6. Zhang P, "Dissecting the single-cell transcriptome network underlying gastric premalignant lesions and early gastric cancer", Cell Rep, 27, pp.1934~1947 (2019)
  7. Ayanbule F, "GATA factors in gastrointestinal malignancy", World J Surg, 35, pp.1757~1765 (2011)
  8. Tremblay M, "GATA transcription factors in development and disease", Development, 145, pp.dev164384~ (2018)
  9. Kohlnhofer BM, "GATA4 regulates epithelial cell proliferation to control intestinal growth and development in mice", Cell Mol Gastroenterol Hepatol, 2, pp.189~209 (2016)
  10. Walker EM, "GATA4 and GATA6regulate intestinal epithelial cytodifferentiation during development", Dev Biol, 392, pp.283~294 (2014)
  11. Haveri H, "Transcription factors GATA-4 and GATA-6 in normal and neoplastic human gastrointestinal mucosa", BMC Gastroenterol, 8, pp.9~ (2008)
  12. Battista S, "Molecular alterations in gastric preneoplastic lesions and early gastric cancer", Int J Mol Sci, 22, pp.6652~ (2021)
  13. Audie JP, "Expression of human mucin genes in respiratory, digestive, and reproductive tracts ascertained by in situ hybridization", J Histochem Cytochem, 41, pp.1479~1485 (1993)
  14. Ho SB, "Expression cloning of gastric mucin complementary DNA and localization of mucin gene expression", Gastroenterology, 109, pp.735~747 (1995)
  15. Reis CA, "Intestinal metaplasia of human stomach displays distinct patterns of mucin(MUC1, MUC2, MUC5AC, and MUC6)expression", Cancer Res, 59, pp.1003~1007 (1999)
  16. Buisine MP, "Mucin gene expression in human embryonic and fetal intestine", Gut, 43, pp.519~524 (1998)
  17. Van Seuningen I, "Transcriptional regulation of the 11p15 mucin genes : towards new biological tools in human therapy, in inflammatory diseases and cancer?", Front Biosci, 6, pp.D1216~D1234 (2001)
  18. van der Sluis M, "The murine Muc2 mucin gene is transcriptionally regulated by the zincfinger GATA-4 transcription factor in intestinal cells", Biochem Biophys Res Commun, 325, pp.952~960 (2004)
  19. Jiang JX, "Risk factors for intestinal metaplasia in a southeastern Chinese population : an analysis of 28, 745 cases", J Cancer Res Clin Oncol, 143, pp.409~418 (2017)
  20. Tatsugami M, "Bile acid promotes intestinal metaplasia and gastric carcinogenesis", Cancer Epidemiol Biomarkers Prev, 21, pp.2101~2107 (2012)
  21. Li T, "MicroRNA-92a-1-5p increases CDX2 by targeting FOXD1 in bile acids-induced gastric intestinal metaplasia", Gut, 68, pp.1751~1763 (2019)
  22. Lu W, "Resveratrol inhibits bile acidinduced gastric intestinal metaplasia via the PI3K", AKT, Phytother Res, pp.2021, 35[DOI]
  23. Yu JH, "Bile acids promote gastric intestinal metaplasia by upregulating CDX2 and MUC2 expression via the FXR", NF-κB signalling pathway, 2019, pp.54, 879~892
  24. Silberg DG, "Cdx1 and Cdx2expression during intestinal development", Gastroenterology, 119, pp.961~971 (2000)
  25. Yamamoto H, "Homeodomain protein CDX2 regulates goblet-specific MUC2 gene expression", Biochem Biophys Res Commun, 300, pp.813~818 (2003)
  26. Yuan T, "SOX2 interferes with the function of CDX2 in bile acid-induced gastric intestinal metaplasia", Cancer Cell Int, 19, pp.24~ (2019)
  27. Zhou H, "Activation of FXR promotes intestinal metaplasia of gastric cells via SHP-dependent upregulation of the expression of CDX2", Oncol Lett, 15, pp.7617~7624 (2018)
  28. Merga YJ, "Importance of the alternative NF-κB activation pathway in inflammationassociated gastrointestinal carcinogenesis", Am J Physiol Gastrointest Liver Physiol, 310, pp.G1081~G1090 (2016)
  29. Gambhir S, "Nuclear factor kappa B role in inflammation associated gastrointestinal malignancies", World J Gastroenterol, 21, pp.3174~3183 (2015)
  30. Kasperczyk H, "Betulinic acid as new activator of NF-kappaB : molecular mechanisms and implications for cancer therapy", Oncogene, 24, pp.6945~6956 (2005)
  31. Kundu S, "Cross-talk between bile acids and gastrointestinal tract for progression and development of cancer and its therapeutic implications", IUBMB Life, 67, pp.514~523 (2015)
  32. Bernstein H, "Bile acids as carcinogens in human gastrointestinal cancers", Mutat Res, 589, pp.47~65 (2005)
  33. Souza RF, "Acid, bile, and CDX : the ABCs of making Barrett's metaplasia", Am J Physiol Gastrointest Liver Physiol, 295, pp.G211~G218 (2008)
  34. Tamagawa Y, "Bile acids induce delta-like 1 expression via Cdx2-dependent pathway in the development of Barrett's esophagus", Lab Invest, 96, pp.325~337 (2016)
  35. Matsuhisa T, "Relation between bile acid reflux into the stomach and the risk of atrophic gastritis and intestinal metaplasia : a multicenter study of 2283cases", Dig Endosc, 25, pp.519~525 (2013)
  36. Bai Y, "Distinct expression of CDX2 and GATA4", 5, development-related genes, in human gastric cancer cell lines, 2000, pp.28, 184~188
  37. Chia NY, "Regulatory crosstalk between lineage-survival oncogenes KLF5, GATA4 and GATA6cooperatively promotes gastric cancer development", Gut, 64, pp.707~719 (2015)
  38. Thompson CA, "Patterning the gastrointestinal epithelium to confer regional-specific functions", Dev Biol, 435, pp.97~108 (2018)
  39. Woodfint RM, "Identification of the MUC2 promoter as a strong promoter for intestinal gene expression through generation of transgenic quail expressing GFP in gut epithelial cells", Int J Mol Sci, 18, pp.196~ (2017)
  40. He Q, "Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia : a review", Cell Death Discov, 8, pp.158~ (2022)
  41. Wang N, "Bile acids increase intestinal marker expression via the FXR", SNAI2, Cell Oncol(Dordr), pp.2021, 44[DOI]
  42. Hoesel B, "The complexity of NF-κB signaling in inflammation and cancer", Mol Cancer, 12, pp.86~ (2013)
  43. Sarkar FH, "NF-kappaB signaling pathway and its therapeutic implications in human diseases", Int Rev Immunol, 27, pp.293~319 (2008)
  44. Xiang Q, "The zinc finger protein GATA4induces mesenchymal-to-epithelial transition and cellular senescence through the nuclear factor-κB pathway in hepatocellular carcinoma", J Gastroenterol Hepatol, 34, pp.2196~2205 (2019)
  45. Benoit YD, "Cooperation between HNF-1alpha, Cdx2, and GATA-4 in initiating an enterocytic differentiation program in a normal human intestinal epithelial progenitor cell line", Am J Physiol Gastrointest Liver Physiol, 298, pp.G504~G517 (2010)
  46. Boudreau F, "Hepatocyte nuclear factor-1 alpha, GATA-4, and caudal related homeodomain protein Cdx2 interact functionally to modulate intestinal gene transcription : implication for the developmental regulation of the sucrase-isomaltase gene", J Biol Chem, 277, pp.31909~31917 (2002)

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