MicroRNA-214-3p modified tetrahedral framework nucleic acids target survivin to induce tumour cell apoptosis
MicroRNA-214-3p modified tetrahedral framework nucleic acids target survivin to induce tumour cell apoptosis
复制标题
MicroRNA-214-3p 修饰的四面体框架核酸靶向存活蛋白以诱导肿瘤细胞凋亡。
DOI：
10.1111/cpr.12708
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发表时间：
2019-10-23
影响因子：
8.5
通讯作者：
Cai, Xiaoxiao
中科院分区：
文献类型：
--
作者：
Li, Songhang;Sun, Yue;Cai, Xiaoxiao
目的由于microRNA的不稳定性，限制了microRNA的应用。因此，我们利用四面体框架核酸和靶向microRNA形成稳定的纳米复合物，以探讨这种纳米复合物是否能促进肿瘤细胞凋亡。将能降低survivin表达的miRNA-214- 3 p修饰到四面体框架核酸上，从而在细胞内递送时产生存活素表达的减少，并最终导致肿瘤细胞凋亡。microRNA-四面体框架核酸载体系统的构建，证明了该载体系统的优越性。流式细胞仪检测结果显示，经该复合物处理后，miRNA-214- 3 p-四面体框架核酸组中处于凋亡晚期和早期的A549细胞比例增加了一倍，细胞周期处于G2-M期的细胞比例下降。抗凋亡蛋白表达的减少和促凋亡蛋白表达的增加表明，这种复合物在细胞中发挥作用的能力，也使它作为一种新的靶向治疗cancer.ConclusionThe肿瘤细胞和胚胎细胞中的独特表达的生存素microRNA四面体框架核酸使一个新的靶向治疗。此外，由于microRNA的功能多样性，这种递送系统方法可以应用于多种领域，如靶向治疗和组织再生。
ObjectivesDue to the instability of microRNAs, the applications of microRNA are currently limited. Thus, we utilized tetrahedral framework nucleic acids and a targeted microRNAs to form a stable nanocomposite to explore whether this nanocomposite can promote apoptosis of tumour cells.Materials and methodsIn our study, the survivin gene, which is expressed only in tumour cells and embryonic cells, was selected as the target gene; miRNA-214-3p, which can reduce the expression of survivin, was modified onto tetrahedral framework nucleic acid, thereby producing a reduction in the expression of survivin upon intracellular delivery and eventually leading to tumour cell apoptosis.ResultsBy comparing the stability of microRNAs with that of microRNA-tetrahedral framework nucleic acid, we proved the superiority of this carrier system. The results of flow cytometry showed that after treated with this complex, the ratio of A549 cells in both late and early period of apoptosis in miRNA-214-3p-tetrahedral framework nucleic acid group had doubled and the cell cycle in the G2-M phase had declined. The decrease in the expression of anti-apoptotic protein and the increase in the expression of pro-apoptotic protein indicate that the ability of this complex to function in cells also makes it attractive as a new targeted therapy for cancer.ConclusionThe unique expression of survivin in tumour cells and embryonic cells makes microRNA-tetrahedral framework nucleic acid a new targeted therapy. In addition, due to the functional diversity of microRNAs, this delivery system approach can be applied to a wide variety of fields, such as targeted therapy and tissue regeneration.