title: Gene regulation mediated by microRNAs in response to green tea polyphenol EGCG in mouse lung cancer.
abstract: BACKGROUND
  Epigallocatechin-3-gallate (EGCG) has been demonstrated to inhibit cancer in experimental studies through its antioxidant activity and modulations on cellular functions by binding specific proteins. We demonstrated previously that EGCG upregulates the expression of microRNA (i.e. miR-210) by binding HIF-1α, resulting in reduced cell proliferation and anchorage-independent growth. However, the binding affinities of EGCG to HIF-1α and many other targets are higher than the EGCG plasma peak level in experimental animals administered with high dose of EGCG, raising a concern whether the microRNA regulation by HIF-1α is involved in the anti-cancer activity of EGCG in vivo.
  
  
  RESULTS
  We employed functional genomic approaches to elucidate the role of microRNA in the EGCG inhibition of tobacco carcinogen-induced lung tumors in A/J mice. By analysing the microRNA profiles, we found modest changes in the expression levels of 21 microRNAs. By correlating these 21 microRNAs with the mRNA expression profiles using the computation methods, we identified 26 potential targeted genes of the 21 microRNAs. Further exploration using pathway analysis revealed that the most impacted pathways of EGCG treatment are the regulatory networks associated to AKT, NF-κB, MAP kinases, and cell cycle, and the identified miRNA targets are involved in the networks of AKT, MAP kinases and cell cycle regulation
  
  
  CONCLUSIONS
  These results demonstrate that the miRNA-mediated regulation is actively involved in the major aspects of the anti-cancer activity of EGCG in vivo.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.forename: Jayson X
authors.initials: JX
authors.lastname: Chen
authors.forename: Chung S
authors.initials: CS
authors.lastname: Yang
authors.forename: Mary Qu
authors.initials: MQ
authors.lastname: Yang
authors.forename: Youping
authors.initials: Y
authors.lastname: Deng
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D028241:Camellia sinensis / Q000737:chemistry*; D002273:Carcinogens; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009602:Nitrosamines; D059808:Polyphenols / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D002273:Carcinogens; D018797:Cell Cycle Proteins; D035683:MicroRNAs; D016328:NF-kappa B; D009602:Nitrosamines; D059808:Polyphenols; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D002392:Catechin; C045651:epigallocatechin gallate; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases