Microrna-23a Regulates Cell Migration And Invasion By Target Pten In Gastric Cancer

INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY(2016)

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摘要
Objective: To investigate the biological significance of abundant miR-23a expression in gastric cancer (GC) and its correlation with PTEN in the pathogenesis of GC migration and invasion. Methods: The human gastric cancer cell lines SGC-7901, AGS, the immortalized cell line GES-1 derived from normal gastric mucosa. Cell transfection and selection of stable cell lines and the gene and protein levels of miR-23a and PTEN were examined to determine the molecular relationship between them in the pathogenesis of gastric cancer. Results: Inhibition of miR-23a effectively reduced migration and invasion of GC cell lines. Bioinformatics and luciferase reporter assay revealed that miR-23a specifically targeted the 3'-UTR of PTEN and regulated its expression. Down-regulation of PTEN enhanced migration and invasion of GC cell lines. Furthermore, in tumor tissues obtained from gastric cancer patients, the expression of miR-23a was negatively correlated with PTEN and the high expression of miR-23a combined with low expression of PTEN might serve as a risk factor for cancer patients. Besides, miR-23a-mediated suppression of PTEN led to activation of AKT/ERK pathways and epithelial-mesenchymal transition (EMT) in GC cells, and finally enhances the activity of GC cell proliferation and movement and promotes GC xenograft tumor growth in mouse models. Conclusion: Our study showed that miR-23a, by down-regulation PTEN, enhances migration and invasion in GC cells.
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关键词
Gastric cancer (GC), PTEN, epithelial-mesenchymal transition (EMT), invasion, migration, target therapy
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