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作 者:陶涵金 陈冉 高崎 TAO Han-Jin;CHEN Ran;GAO Qi(School of Pharmacy,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Shanghai Xingling Science and Technology Pharmaceutical Co.,Ltd,Shanghai 201703,China)
机构地区:[1]上海中医药大学中药学院,上海201203 [2]上海上药杏灵科技药业股份有限公司,上海201703
出 处:《中国生物化学与分子生物学报》2023年第12期1685-1695,共11页Chinese Journal of Biochemistry and Molecular Biology
基 金:高崎上海市中药专家传承工作室(No.2020ZYGZS-010)资助。
摘 要:MicroRNAs(miRNAs)是一类19~24个核苷酸的非编码内源性小分子RNA,功能研究表明,miRNAs参与所有细胞过程的调节,包括生长发育、分化凋亡、炎症、免疫应答、代谢及信号转导等生物学过程。最近研究发现,植物miRNAs作为一类功能广泛的分子调控因子,不仅调控植物自身基因的表达,外源植物miRNAs还通过饮食进入到哺乳动物细胞中,调节某些与人类疾病治疗相关的基因或生物学过程。一些植物miRNAs由于其3′端存在2′-O-甲基化修饰、独特茎环结构、高GC含量以及微囊泡、RNA结合蛋白或外泌体样纳米颗粒等载体对其的保护作用,从而在食物加工与极端胃肠道环境中能保持高度稳定。植物miRNAs主要通过饮食获取,借助跨膜miRNA转运蛋白质、受体介导的内吞作用、肠上皮细胞间隙扩散、肠道微生物群脂质依赖性摄取等不同的转运机制,其被消化系统吸收后进入体循环并递送至器官组织,再调节受体细胞功能。本文综述了植物来源miRNAs的跨界调控研究现状,详细总结了植物miRNAs抵抗降解的可能方法、跨越胃肠道屏障的转运机制以及被摄入后在哺乳动物体内的调控作用,例如抗炎、抗病毒和抗肿瘤等相关发现,揭示植物miRNAs在基于RNA的分子治疗以及开发新的治疗药物等方面具有很高的应用潜力。MicroRNAs(miRNAs)are a class of 19~24 nucleotide non-coding endogenous small molecule RNAs.Functional studies have shown that miRNAs are involved in the regulation of all cellular processes,including growth and development,differentiation,apoptosis,inflammation,immune response,metabolism,signal transduction as well as other biological processes.Recently,miRNAs from plants are found to be such versatile molecular regulators that they not only regulate their own gene expression,but by dietary intake they can migrate into mammalian cells and regulate certain genes or biological processes that are involved in treating human diseases.Certain plant miRNAs have 2′-O-methylated modified 3′ends,unique stem-loop structures,high GC contents,as well as protection by microvesicles,RNA-binding proteins or exosome-like nanoparticles,all of which give them high stability under food processing and the extreme environment in gastrointestinal tracts.Plant miRNAs that are mainly obtained through oral food intake can be absorbed by the digestive system via different transport mechanisms like membrane transport proteins,receptor-mediated endocytosis,diffusion in the space between intestinal epithelial cells,lipid-dependent uptake of the gut bacteria and so on.Then they get into the circulatory system and are delivered to organ tissues and regulate the functions of recipient cells.This review summarizes the current knowledge of cross-kingdom regulation by plant miRNAs,including possible ways of enhancing their resistance to degradation,their transport mechanisms across the gastrointestinal barrier and regulation effects(anti-inflammation,antiviral,anticancer,etc.)in mammals after ingestion.It reveals that plant-derived miRNAs can be well applied in RNA-based molecular therapies and the development of new therapeutic agents.
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