MicroRNA-21 Regulates the Proliferation and Invasion in Esophageal Squamous Cell Carcinoma

被引：238

作者：

Hiyoshi, Yukiharu ^{[1
]}

Kamohara, Hidenobu ^{[1
]}

Karashima, Ryuichi ^{[1
]}

Sato, Nobutaka ^{[1
]}

Imamura, Yu ^{[1
]}

Nagai, Youhei ^{[1
]}

Yoshida, Naoya ^{[1
]}

Toyama, Eiichiro ^{[1
]}

Hayashi, Naoko ^{[1
]}

Watanabe, Masayuki ^{[1
]}

Baba, Hideo ^{[1
]}

机构：

[1] Kumamoto Univ, Grad Sch Med Sci, Dept Surg Gastroenterol, Kumamoto 8608556, Japan

来源：

CLINICAL CANCER RESEARCH | 2009年 / 15卷 / 06期

关键词：

TUMOR-SUPPRESSOR GENE; EXPRESSION PROFILES; TRANSFORMATION SUPPRESSOR; ALTERED EXPRESSION; DOWN-REGULATION; MICRO-RNA; CANCER; MIR-21; PDCD4; TRANSLATION;

D O I：

10.1158/1078-0432.CCR-08-2545

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: MicroRNAs are similar to 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.

引用

页码：1915 / 1922

页数：8

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