title: Epigenetic silencing of microRNA-375 regulates PDK1 expression in esophageal cancer.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are a class of small (19-25 nucleotides) noncoding RNAs that regulate the expressions of a wide variety of genes, including some involved in cancer development. Some recent studies show that DNA methylation contributes to down-regulation of microRNA-375 (miR-375) during tumorigenesis. Whether or not down-regulation of miR-375 also exists in esophageal cancer is unknown.
  
  
  OBJECTIVE
  Our aim was to test the hypothesis that down-regulation of miR-375 also exists in esophageal cancer.
  
  
  METHODS
  Expression of levels of miR-375 were examined using real-time PCR on paired esophageal cancer and adjacent non-cancerous tissues. The methylation status is detected by methylation specific-PCR (MSP).
  
  
  RESULTS
  The results show that miR-375 is downregulated by hypermethylation of the promoter in esophageal cancer tissues. Epigenetic silencing of miR-375 induced an up-regulation of its targets, 3-phosphoinositide-dependent protein kinase-1 (PDK1). Restoration of the miR-375 expression in esophageal cancer cell lines downregulated the PDK1 expression. Furthermore, the miR-375 expression was found to be inversely correlated with PDK1 expression in esophageal cancer.
  
  
  CONCLUSIONS
  Thus, miR-375 is frequently down-regulated in esophageal cancer and is a negative regulator of PDK1.
authors.affiliation: Department of Gerontology, The First Affiliated Hospital, Zhengzhou University, Institute of Clinical Medical Research of Universities in Henan Province, 1 East Jianshe Road, Zhengzhou, Henan Province, People's Republic of China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: Lin
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Li
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases; D017209:Apoptosis / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation / Q000502:physiology; D004273:DNA, Neoplasm / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology; D044127:Epigenesis, Genetic / Q000235:genetics / Q000502:physiology*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology
chemical_list: D004273:DNA, Neoplasm; C540933:MIRN375 microRNA, human; D035683:MicroRNAs; D064413:3-Phosphoinositide-Dependent Protein Kinases; C578562:PDPK1 protein, human; D017346:Protein Serine-Threonine Kinases