Delivery of microRNA-21-sponge and pre-microRNA-122 by MS2 virus-like particles to therapeutically target hepatocellular carcinoma cells
Delivery of microRNA-21-sponge and pre-microRNA-122 by MS2 virus-like particles to therapeutically target hepatocellular carcinoma cells
复制标题
通过 MS2 病毒样颗粒递送 microRNA-21-海绵和 pre-microRNA-122 以治疗性靶向肝细胞癌细胞
DOI：
10.1177/15353702211035689
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发表时间：
2021-10-13
影响因子：
3.2
通讯作者：
Li, Jinming
中科院分区：
文献类型：
--
作者：
Zhang, Jiawei;Li, Dandan;Li, Jinming
microrna与肝细胞癌的发展有关，可以作为潜在的治疗靶点。增加肿瘤抑制microrna和减少致癌microrna的治疗策略已经被开发出来。本文研究了利用MS2病毒样颗粒同时改变两种microrna的效果。将microRNA-21-sponge序列与pre-microRNA-122序列连接并克隆成病毒样颗粒表达载体。制备了含有microrna -21海绵和预microrna -122序列的病毒样颗粒，并与靶向肝癌细胞的细胞特异性肽交联。利用RT-qPCR和功能分析研究递送效应，研究靶mrna水平、细胞毒性以及增殖、侵袭和迁移的影响。病毒样颗粒将miR-21-sponge送入细胞，Ct值最高可达10。连接的pre-miR-122被加工成成熟的miR-122。miR-21 mRNA靶点如预测的那样下调，上调1.2 - 2.8倍，蛋白表达相应升高。miR-21-sponge可抑制HCC细胞的增殖、迁移和侵袭。同时递送miR-21-sponge和miR-122进一步降低增殖、迁移和侵袭，分别高达34%、63%和65%。联合用药可促进肝癌细胞凋亡。综上所述，利用细胞特异性肽修饰的病毒样颗粒递送mir -21-海绵和miR-122是一种有效且方便的纠正肝癌细胞microRNA失调的策略，是一种有前景的肝癌治疗策略。
MicroRNAs are related to the development of hepatocellular carcinoma and can serve as potential therapeutic targets. Therapeutic strategies increasing tumor-suppressive microRNAs and reducing oncogenic microRNAs have been developed. Herein, the effects of simultaneously altering two microRNAs using MS2 virus-like particles were studied. The sequences of microRNA-21-sponge and pre-microRNA-122 were connected and cloned into a virus-like particle expression vector. Virus-like particles containing microRNA-21-sponge and pre-microRNA-122 sequences were prepared and crosslinked with a cell-specific peptide targeting hepatocellular carcinoma cells. Delivery effects were studied using RT-qPCR and functional assays to investigate the level of target mRNAs, cell toxicity, and the effects of proliferation, invasion, and migration. Virus-like particles delivered miR-21-sponge into cells, with the Ct value reaching 10 at most. The linked pre-miR-122 was processed into mature miR-122. The mRNA targets of miR-21 were derepressed as predicted and upregulated 1.2–2.8-fold, and the expression of proteins was elevated correspondingly. Proliferation, migration, and invasion of HCC cells were inhibited by miR-21-sponge. Simultaneous delivery of miR-21-sponge and miR-122 further decreased proliferation, migration, and invasion by up to 34%, 63%, and 65%, respectively. And the combination promoted the apoptosis of HCC cells. In conclusion, delivering miR-21-sponge and miR-122 using virus-like particles modified by cell-specific peptides is an effective and convenient strategy to correct microRNA dysregulation in hepatocellular carcinoma cells and is a promising therapeutic strategy for hepatocellular carcinoma.