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

作者：Hiyoshi Yukiharu; Kamohara Hidenobu; Karashima Ryuichi; Sato Nobutaka; Imamura Yu; Nagai Youhei; Yoshida Naoya; Toyama Eiichiro; Hayashi Naoko; Watanabe Masayuki; Baba Hideo^*

来源：Clinical Cancer Research, 2009, 15(6): 1915-1922.

DOI：10.1158/1078-0432.CCR-08-2545

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.

• 出版日期2009-3-15