title: The prognostic and chemotherapeutic value of miR-296 in esophageal squamous cell carcinoma.
abstract: OBJECTIVE
  We aimed first to investigate the expression pattern of miRNAs in esophageal squamous cell cancer and then compared it with those of adjacent benign esophageal tissues. The role of target miRNAs in the development of esophageal cancer was further detected.
  
  
  BACKGROUND
  Although esophageal squamous cell carcinoma was of high incidence in China, the pathogenic mechanism remained largely unknown. A better understanding of changes in miRNA expression during esophageal carcinogenesis might lead to possible improvements in the diagnosis and treatment for esophageal carcinoma.
  
  
  METHODS
  The miRNAs were identified differentially expressed in esophageal cancer tissues, using miRNA microarray, real-time PCR, and Northern blot. The role of target miRNAs was investigated by in vitro and in vivo assay.
  
  
  RESULTS
  Nine miRNAs with increased expression and 3 with decreased expression were identified. The expression of miR-296 was found increasingly up-regulated in esophagitis tissues, esophageal carcinoma in situ, and esophageal squamous cell cancer tissues. Low expression of miR-296 was able to distinguish long-term survivors with node-positive disease from those dying within 20 months by predicting survival (median, 23.7 vs. 12.9 months). Downregulation of miR-296 might inhibit growth of esophageal cancer cells in vitro and in vivo through regulation of cyclin D1 and p27. Downregulation of miR-296 could confer sensitivity of both P-glycoprotein-related and P-glycoprotein-nonrelated drugs on esophageal cancer cells, and might promote ADR-induced apoptosis, accompanied by increased accumulation and decreased releasing amount of ADR. Downregulation of miR-296 could significantly decrease the expression of P-glycoprotein, Bcl-2, and the transcription of MDR1, but up-regulate the expression of Bax.
  
  
  CONCLUSIONS
  MiR-296 might play important roles in the pathogenesis of esophageal cancer and considered as a potential target for this malignancy intervention.
authors.affiliation: Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Shaanxi Province, China. hlhyhj@126.com
authors.forename: Liu
authors.initials: L
authors.lastname: Hong
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhang
authors.forename: Mengbin
authors.initials: M
authors.lastname: Li
authors.forename: Taiqian
authors.initials: T
authors.lastname: Gong
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Kaichun
authors.initials: K
authors.lastname: Wu
authors.forename: Qingchuan
authors.initials: Q
authors.lastname: Zhao
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D049109:Cell Proliferation; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018816:Genes, cdc; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D046228:Microarray Analysis; D011379:Prognosis; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C549871:MIRN296 microRNA, human; D035683:MicroRNAs