School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China.
FEBS Lett. 2014 May 29;588(11):2009-15. doi: 10.1016/j.febslet.2014.04.024. Epub 2014 Apr 29.
To investigate the role of microRNAs in the development of chemoresistance and related epithelial-mesenchymal transition (EMT), we examined the effect of miR-489 in adriamycin (ADM)-resistant human breast cancer cells (MCF-7/ADM). MiR-489 was significantly suppressed in MCF-7/ADM cells compared with chemosensitive parental control MCF-7/WT cells. Forced-expression of miR-489 reversed chemoresistance. Furthermore, Smad3 was identified as the target of miR-489 and is highly expressed in MCF-7/ADM cells. Forced expression of miR-489 both inhibited Smad3 expression and Smad3 related EMT properties. Finally, the interactions between Smad3, miR-489 and EMT were confirmed in chemoresistant tumor xenografts and clinical samples, indicating their potential implication for treatment of chemoresistance.
为了研究 microRNAs 在化疗耐药和相关上皮-间充质转化（EMT）中的作用，我们研究了 miR-489 在阿霉素（ADM）耐药人乳腺癌细胞（MCF-7/ADM）中的作用。与化疗敏感的亲本对照 MCF-7/WT 细胞相比，miR-489 在 MCF-7/ADM 细胞中显著下调。强制表达 miR-489 可逆转化疗耐药性。此外，Smad3 被鉴定为 miR-489 的靶基因，并且在 MCF-7/ADM 细胞中高度表达。强制表达 miR-489 既抑制了 Smad3 的表达，也抑制了 Smad3 相关的 EMT 特性。最后，在化疗耐药的肿瘤异种移植和临床样本中证实了 Smad3、miR-489 和 EMT 之间的相互作用，表明它们在治疗化疗耐药方面具有潜在的意义。
