A plant immune protein enables broad antitumor response by rescuing microRNA deficiency

第一作者：Ye Qi

第一单位：北京大学

通讯作者：Peng Du

 Abstarct 

背景回顾：Cancer cells are featured with uncontrollable activation of cell cycle, and microRNA deficiency drives tumorigenesis. The RNA-dependent RNA polymerase (RDR) is essential for small-RNA-mediated immune response in plantsbut is absent in vertebrates. 

癌细胞的典型特征是细胞周期的不可控激活，而microRNA缺陷则会导致肿瘤发生。RNA依赖型RNA聚合酶（RDR）是植物中由小RNA介导的植物免疫响应所必需的，但其在脊椎动物中则不存在。

主要研究：Here, we show that ectopic expression of plant RDR1 can generally inhibit cancer cell proliferation. 

本文中，作者发现在动物细胞中异位表达植物的RDR1蛋白能够抑制癌细胞的增殖。

结果1-植物RDR1的抗肿瘤机制：In many human primary tumors, abnormal microRNA isoforms with 1-nt-shorter 3′ ends are widely accumulated. RDR1 with nucleotidyltransferase activity can recognize and modify the problematic AGO2-free microRNA duplexes with mononucleotides to restore their 2 nt overhang structure, which eventually rescues AGO2-loading efficiency and elevates global miRNA expression to inhibit cancer cell-cycle specifically. 

在很多人类原发性的肿瘤中，3′末端短1 nt的microRNA广泛积累。RDR1具有核苷酸基转移酶活性，能够识别并对有问题的AGO2-free的microRNA双链体进行单核苷酸修饰，以恢复其2 nt的悬垂结构，从而拯救这些microRNA被装载至AGO2的效率，并提高全域miRNA表达，最终特异性抑制癌细胞周期。

结果2-RDR1广谱抗肿瘤：The broad antitumor effects of RDR1, which can be delivered by an adeno-associated virus, are visualized in multiple xenograft tumor models in vivo. 

通过腺相关病毒运送RDR1蛋白，体内试验表明RDR1存在广谱抗肿瘤活性，在多个异种移植肿瘤模型中均能够发挥作用。

结论：Altogether, we reveal the widespread accumulation of aberrant microRNA isoforms in tumors and develop a plant RDR1-mediated antitumor stratagem by editing and repairing defective microRNAs.

综上，本文的研究揭示了肿瘤中异常microRNA异构体的广泛积累，并开发了一种利用植物RDR1来编辑和修复缺陷型的microRNA，从而达到抗肿瘤的新型策略。

** 杜 鹏 **

doi: https://doi.org/10.1016/j.cell.2022.04.030

Journal: Cell

Published date: May 26, 2022

CITE

Ye Qi, Li Ding, Siwen Zhang, Shengze Yao, Jennie Ong, Yi Li, Hong Wu, Peng Du. A plant immune protein enables broad antitumor response by rescuing microRNA deficiency. Cell, 2022, 185(11): 1888-1904. DOI: https://doi.org/10.1016/j.cell.2022.04.030