Document Detail

MicroRNA-21 regulates the proliferation and invasion in esophageal squamous cell carcinoma.
MedLine Citation:
PMID:  19276261     Owner:  NLM     Status:  MEDLINE    
PURPOSE: MicroRNAs are approximately 22 nucleotide noncoding RNA molecules that posttranscriptionally regulate gene expression. The aim of this study was (a) to determine a role of microRNA-21 in esophageal squamous cell carcinoma and (b) to elucidate the regulation of the programmed cell death 4 (PDCD4) gene by microRNA-21. EXPERIMENTAL DESIGN: MicroRNA-21 expression was investigated in 20 matched normal esophageal epitheliums and esophageal squamous cell carcinomas and seven esophageal squamous cell carcinoma cell lines (TE6, TE8, TE10, TE11, TE12, TE14, KYSE30) by TaqMan quantitative real-time PCR and in situ hybridization. To evaluate the role of microRNA-21, cell proliferation and invasion were analyzed with anti-microRNA-21-transfected cells. In addition, the regulation of PDCD4 by microRNA-21 was elucidated to identify the mechanisms of this regulation. RESULTS: Of 20 paired samples, 18 cancer tissues overexpressed microRNA-21 in comparison with matched normal epitheliums. Specifically, patients with lymph node metastasis or venous invasion showed significantly high expression of microRNA-21. In situ hybridization for microRNA-21 showed strong positive staining in paraffin-embedded esophageal squamous cell carcinoma tissues. All seven esophageal squamous cell carcinoma cell lines also overexpressed microRNA-21, and anti-microRNA-21-transfected cells showed significant reduction in cellular proliferation and invasion. The PDCD4 protein levels in esophageal squamous cell carcinoma cells have an inverse correlation with microRNA-21 expression. Anti-microRNA-21-transfected cells increased PDCD4 protein expression without changing the PDCD4 mRNA level and increased a luciferase-reporter activity containing the PDCD4-3' untranslated region construct. CONCLUSIONS: MicroRNA-21 targets PDCD4 at the posttranscriptional level and regulates cell proliferation and invasion in esophageal squamous cell carcinoma. It may serve as a novel therapeutic target in esophageal squamous cell carcinoma.
Yukiharu Hiyoshi; Hidenobu Kamohara; Ryuichi Karashima; Nobutaka Sato; Yu Imamura; Youhei Nagai; Naoya Yoshida; Eiichiro Toyama; Naoko Hayashi; Masayuki Watanabe; Hideo Baba
Publication Detail:
Type:  Journal Article     Date:  2009-03-10
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  15     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-03-17     Completed Date:  2009-04-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1915-22     Citation Subset:  IM    
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
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MeSH Terms
Aged, 80 and over
Apoptosis Regulatory Proteins / analysis,  genetics
Carcinoma, Squamous Cell / pathology*
Cell Proliferation
Esophageal Neoplasms / pathology*
In Situ Hybridization
MicroRNAs / analysis,  physiology*
Middle Aged
Neoplasm Invasiveness
RNA-Binding Proteins / analysis,  genetics
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/MIRN21 microRNA, human; 0/MicroRNAs; 0/PDCD4 protein, human; 0/RNA-Binding Proteins

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