Li Xiaomei, Liang Jun, Liu Ying-Xun, Wang Yuming, Yang Xiao-Hui, Luan Bao-Hong, Zhang Gui-Ling, Du Juan, Wu Xia-Hong
Pharmazie. 2016 Nov 2;71(11):640-643. doi: 10.1691/ph.2016.6696.
Drug resistance remains a major unresolved obstacle for gastric cancer (GC) treatment. Recently, increasing studies have showen that microRNAs (miRNAs) are involved in cancer chemotherapeutic resistance and can potentially be applied to reverse drug resistance in cancers. The relationship between miRNA-149 expression and cisplatin (DDP) resistance in GC cells is still unknown. Here, we detected miR-149 expression by using RT-PCR and found that expression of miR-149 was downregulated in SGC7901/DDP cells compared with SGC7901cells, indicating a role of miR-149 in determining cisplatin-resistance of GC cells. Then, SGC7901/DDP cells were tansfected with miR-149 mimics, MTT assay was performed to determine SGC7901/DDP cell viability, and showed that overexpression of miR-149 inhibited the cell viability after cisplatin treatment, suggesting that up-regulation of miR-149 enhanced SGC7901/DDP cell sensitivity to cisplatin. Furthermore, we confirmed that Forkhead box M1 (FoxM1) is a direct target of miR-149 in SGC7901/DDP cells by using luciferase reporter assay. Besides, we also demonstrated that miR-149 enhances SGC7901/DDP cell sensitivity to cisplatin by downregulating FoxM1 expression. In summary, our data provide new insights that miR-149 plays an important role in determining sensitivity of cisplatin-resistant GC cells by targeting FoxM1 and suggest that miR-149 could be a potential target for reversing drug resistance in GC.
耐药性仍然是胃癌(GC)治疗中一个主要的未解决障碍。最近,越来越多的研究表明,微小RNA(miRNA)参与癌症化疗耐药,并且有可能用于逆转癌症中的耐药性。miRNA-149表达与GC细胞中顺铂(DDP)耐药性之间的关系仍然未知。在此,我们通过逆转录聚合酶链反应(RT-PCR)检测miR-149的表达,发现与SGC7901细胞相比,SGC7901/DDP细胞中miR-149的表达下调,表明miR-149在决定GC细胞顺铂耐药性中发挥作用。然后,用miR-149模拟物转染SGC7901/DDP细胞,进行MTT试验以确定SGC7901/DDP细胞活力,结果显示miR-149的过表达抑制了顺铂处理后的细胞活力,提示miR-149的上调增强了SGC7901/DDP细胞对顺铂的敏感性。此外,我们通过荧光素酶报告基因试验证实,叉头框M1(FoxM1)是SGC7901/DDP细胞中miR-149的直接靶点。此外,我们还证明miR-149通过下调FoxM1表达增强SGC7901/DDP细胞对顺铂的敏感性。总之,我们的数据提供了新的见解,即miR-149通过靶向FoxM1在决定顺铂耐药GC细胞的敏感性中发挥重要作用,并提示miR-149可能是逆转GC耐药性的潜在靶点。