MicroRNA-196a targets annexin A1: a microRNA-mediated mechanism of annexin A1 downregulation in cancers
| Autor: | Su S. Chen, Bedia A. Barkoh, Madan G. Luthra, Asif Rashid, Russell Broaddus, Dipen M. Maru, Joe Ensor, Angela Romans, Yisheng Li, Rajesh R. Singh, Christina Hannah, Rajyalakshmi Luthra, Constance Albarracin |
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| Rok vydání: | 2008 |
| Předmět: |
endocrine system
Cancer Research medicine.medical_specialty Down-Regulation Biology medicine.disease_cause Annexin RNA interference Cell Line Tumor Neoplasms Internal medicine microRNA Gene expression Genetics medicine Humans Gene silencing Computer Simulation RNA Messenger Molecular Biology Annexin A1 Cell Proliferation Regulation of gene expression Base Sequence Gene Expression Regulation Neoplastic MicroRNAs Endocrinology Cancer research Carcinogenesis |
| Zdroj: | Oncogene. 27:6667-6678 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/onc.2008.256 |
| Popis: | Suppression of annexin A1 (ANXA1), a mediator of apoptosis and inhibitor of cell proliferation, is well documented in various cancers but the underlying mechanism remains unknown. We investigated whether decreased ANXA1 expression was mediated by microRNAs (miRNAs), which are small, non-coding RNAs that negatively regulate gene expression. Using Sanger miRBase, we identified miR-584, miR-196a and miR-196b as potential miRNAs targeting ANXA1. Only miRNA-196a showed significant inverse correlation with ANXA1 mRNA levels in 12 cancer cell lines of esophageal, breast and endometrial origin (Pearson's correlation -0.66, P=0.019), identifying this as the candidate miRNA targeting ANXA1. Inverse correlation was also observed in 10 esophageal adenocarcinomas (Pearson's correlation -0.64, P=0.047). Analysis of paired normal/tumor tissues from additional 10 patients revealed an increase in miR-196a in the cancers (P=0.003), accompanied by a decrease in ANXA1 mRNA (P=0.004). Increasing miR-196a levels in cells by miR-196a mimics resulted in decreased ANXA1 mRNA and protein. In addition, miR-196a mimics inhibited luciferase expression in luciferase plasmid reporter that included predicted miR-196a recognition sequence from ANXA1 3'-untranslated region confirming that miR-196a directly targets ANXA1. miR-196a promoted cell proliferation, anchorage-independent growth and suppressed apoptosis, suggesting its oncogenic potential. This study demonstrated a novel mechanism of post-transcriptional regulation of ANXA1 expression and identified miR-196a as a marker of esophageal cancer. |
| Databáze: | OpenAIRE |
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