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Updated: Jun 25, 2026

Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
Published on: April 6, 2012
MicroRNA-21 regulates the proliferation and invasion in esophageal squamous cell carcinoma
Yukiharu Hiyoshi1, Hidenobu Kamohara, Ryuichi Karashima
1Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
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.
Insights
MicroRNA-21 is overexpressed in esophageal squamous cell carcinoma, promoting cancer cell proliferation and invasion. Targeting microRNA-21 may offer a new therapeutic strategy for this disease.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- MicroRNAs are key regulators of gene expression.
- Esophageal squamous cell carcinoma (ESCC) is a significant global health concern.
- Understanding molecular mechanisms driving ESCC is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role of microRNA-21 (miR-21) in ESCC.
- To determine if miR-21 regulates the programmed cell death 4 (PDCD4) gene.
- To explore miR-21 as a potential therapeutic target in ESCC.
Main Methods:
- Quantitative real-time PCR and in situ hybridization were used to assess miR-21 expression in ESCC tissues and cell lines.
- Cell proliferation and invasion assays were performed using anti-miR-21-transfected cells.
- Western blotting and luciferase reporter assays were employed to elucidate the regulatory mechanism of PDCD4 by miR-21.
Main Results:
- miR-21 was significantly overexpressed in 18 of 20 ESCC tissues compared to normal samples.
- High miR-21 expression correlated with lymph node metastasis and venous invasion.
- Inhibition of miR-21 reduced ESCC cell proliferation and invasion, and increased PDCD4 protein levels, suggesting posttranscriptional regulation.
Conclusions:
- miR-21 directly targets PDCD4 at the posttranscriptional level.
- miR-21 plays a critical role in regulating cell proliferation and invasion in ESCC.
- miR-21 represents a promising therapeutic target for ESCC treatment.
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