miR-27b and miR-34a enhance docetaxel sensitivity of prostate cancer cells through inhibiting epithelial-to-mesenchymal transition by targeting ZEB1 - 31/12/17
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Abstract |
Docetaxel resistance is a primary clinical obstacle in the therapy of advanced prostate cancer (PCa). Aberrant expression of miR-27b and miR-34a has been revealed to be implicated in drug resistance of different tumors. Nevertheless, the roles of miR-27b and miR-34a in docetaxel resistance of PCa and their molecular mechanisms are far from being elucidated. In this study, we found that miR-27b and miR-34a were significantly downregulated in docetaxel-resistant PCa cells. Gain-of-function experiments showed that overexpression of miR-27b or miR-34a enhanced docetaxel sensitivity and inhibited EMT in docetaxel-resistant PCa cells. Moreover, miR-27b and miR-34a was demonstrated to directly target ZEB1 and suppress ZEB1 expression. Loss-of-function analysis disclosed that ZEB1 knockdown enhanced docetaxel sensitivity and suppressed EMT in docetaxel-resistant PCa cells. Rescue experiments presented that ZEB1 overexpression abolished the effects of miR-27b or miR-34a overexpression on docetaxel sensitivity and EMT in docetaxel-resistant PCa cells. Finally, Tumor xenograft assay confirmed the contribution of miR-27b and miR-34a in improving docetaxel sensitivity in PCa in vivo. In summary, miR-27b and miR-34a overexpression enhanced docetaxel sensitivity of PCa partly through inhibiting EMT by targeting ZEB1, providing new insights into the molecular mechanism of miR-27b and miR-34a in modulating docetaxel resistance and potential therapy targets in advanced PCa.
Le texte complet de cet article est disponible en PDF.Abbreviations : PCa, CRPC, miRNAs, EMT, snRNA, PVDF
Keywords : MiR-27b, miR-34a, Docetaxel sensitivity, ZEB1, EMT, Prostate cancer
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Vol 97
P. 736-744 - janvier 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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