4.6 Article

MicroRNA-23a enhances migration and invasion through PTEN in osteosarcoma

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CANCER GENE THERAPY
卷 22, 期 7, 页码 351-359

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NATURE PUBLISHING GROUP
DOI: 10.1038/cgt.2015.27

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To investigate the biological significance of abundant rnicroRNA-23a (miR-23a) expression in osteosarcoma and its correlation with PTEN in the pathogenesis of osteosartoma migration and invasion. The human osteosarcorna cell lines MG63, HOS58 and SaoS-2, and the human normal osteoblasts (hF081.19) were grown in RPMI 1640 medium supplemented with 10% fetal bovine serum. Gene and protein levels of miR-23a and PTEN were examined to determine the molecular relatioriship between them in the pathogenesis of osteosarcoma. Inhibition of miR-23a effectively reduced migration and invasion of osteosarcoma cell lines. Bioinfortnatics and luciferase-reporter assay revealed that miR-23a specifically targeted the 3'-untranslational region of PTEN and regulated its expression. Dowriregulation of PTEN enhanced migration and invasion of osteosarconla cell lines. Furthermore, in tumor tissues obtained from osteosarcoma 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 osteosarcoma cells, and finally enhanced the activity of osteosarcoma cell proliferation, and movement and promoted osteosarcoma xenograft tumor growth in mouse models. Our study showed that milk-23a, by downregulatibn of PTEN, enhanced migration and invasion in osteosarcoma cells.

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