Liposome-lentivirus for miRNA therapy with molecular mechanism study

文献类型： 外文期刊

第一作者： Sun, Fen

作者： Sun, Fen;Sun, Fen;Chen, Huaqing;Dai, Xiaoyong;Li, Jing;Huang, Laiqiang;Chen, Huaqing;Hou, Yibo;Li, Jing;Huang, Laiqiang;Dai, Xiaoyong;Zhang, Yinghe;Guo, Bing;Guo, Bing;Yang, Dongye

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关键词： LCSCs; miR-145-5p; Autophagy; GSK3 beta/Wnt/beta-catenin

期刊名称：JOURNAL OF NANOBIOTECHNOLOGY （ 影响因子：10.6； 五年影响因子：11.4 ）

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年卷期： 2024 年 22 卷 1 期

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收录情况： SCI

摘要： Background Cancer stem cells (CSCs) play a vital role in the occurrence, maintenance, and recurrence of solid tumors. Although, miR-145-5p can inhibit CSCs survival, poor understanding of the underlying mechanisms hamperes further therapeutic optimization for patients. Lentivirus with remarkable transduction efficiency is the most commonly used RNA carrier in research, but has shown limited tumor-targeting capability.Methods We have applied liposome to decorate lentivirus surface thereby yielding liposome-lentivirus hybrid-based carriers, termed miR-145-5p-lentivirus nanoliposome (MRL145), and systematically analyzed their potential therapeutic effects on liver CSCs (LCSCs).Results MRL145 exhibited high delivery efficiency and potent anti-tumor efficacy under in vitro and in vivo. Mechanistically, the overexpressed miR-145-5p can significantly suppress the self-renewal, migration, and invasion abilities of LCSCs by targeting Collagen Type IV Alpha 3 Chain (COL4A3). Importantly, COL4A3 can promote phosphorylating GSK-3 beta at ser 9 (p-GSK-3 beta S9) to inactivate GSK3 beta, and facilitate translocation of beta-catenin into the nucleus to activate the Wnt/beta-catenin pathway, thereby promoting self-renewal, migration, and invasion of LCSCs. Interestingly, COL4A3 could attenuate the cellular autophagy through modulating GSK3 beta/Gli3/VMP1 axis to promote self-renewal, migration, and invasion of LCSCs.Conclusions These findings provide new insights in mode of action of miR-145-5p in LCSCs therapy and indicates that liposome-virus hybrid carriers hold great promise in miRNA delivery.

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