MicroRNA-21 regulates the proliferation and invasion in esophageal squamous cell carcinoma
Abstract
Purpose: MicroRNAs are ∼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.
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PDCD4 loss is diagnostic for human cancer staging and prognostic for survival in colon, lung, liver, breast, glioma and esophageal cancers.
“its loss is diagnostic for human cancer staging and prognostic for survival in colon, lung, liver, breast, glioma and esophageal cancers (6–11).”
From Tumor suppressor PDCD4 inhibits NF-κB-dependent transcription in human glioblastoma cells by direct interaction with p65 (2014) · cites this paper as [9]
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- Authors
- Hiyoshi, Y., Kamohara, H., Karashima, R., Sato, N., Imamura, Y., Nagai, Y., Yoshida, N., Toyama, E., Hayashi, N., Watanabe, M., & Baba, H.
- Affiliations
- Kumamoto University (JP)
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2009-03-15
- Volume
- 15
- Issue
- 6
- Pages
- 1915-1922
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2163578933
- Cited by
- 269
- References
- 6
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 6 · 2021: 12 · 2020: 14 · 2019: 4 · 2018: 15 · 2017: 18 · 2016: 32 · 2015: 22 · 2014: 24 · 2013: 23 · 2012: 27
- FWCI
- 10.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Health Sciences › Medicine › Surgery › Esophageal Cancer Research and Treatment
- Keywords
- miR-21, esophageal squamous cell carcinoma, PDCD4, cell proliferation, tumor invasion, lymph node metastasis, venous invasion, post-transcriptional regulation, 3' untranslated region, therapeutic target
- MeSH terms
- Aged, Aged, 80 and over, Carcinoma, Squamous Cell, Esophageal Neoplasms, Female, Humans, Male, Middle Aged, Neoplasm Invasiveness, RNA-Binding Proteins, In Situ Hybridization, MicroRNAs, Cell Proliferation, Apoptosis Regulatory Proteins
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