A-to-I-edited miRNA-379-5p inhibits cancer cell proliferation through CD97-induced apoptosis
A-to-I-edited miRNA-379-5p inhibits cancer cell proliferation through CD97-induced apoptosis
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A-to-I 编辑的 miRNA-379-5p 通过 CD97 诱导的细胞凋亡抑制癌细胞增殖。
DOI：
10.1172/jci123396
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发表时间：
2019-12-02
影响因子：
15.9
通讯作者：
Liang, Han
中科院分区：
文献类型：
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作者：
Xu, Xiaoyan;Wang, Yumeng;Liang, Han
MiRNAs和A-to-I RNA编辑，一种广泛的核苷酸修饰机制，最近都成为癌症病理生理学中的关键角色。然而，对miRNAs的RNA编辑在癌症中的功能影响在很大程度上仍未被探索。在这里，我们关注的是miR-379-5P种子区中由ADAR2催化的RNA编辑位点。与正常组织相比，该网站在肿瘤中编辑不足，高编辑水平与不同癌症类型的患者更好的生存时间相关。我们证明，与野生型miRNA相比，编辑后的miR-379-5p在体外不同的肿瘤环境中抑制细胞增殖并促进细胞凋亡，这是由于编辑后的miR-379-5p具有靶向CD97的能力，而不是野生型miR-379-5p。重要的是，通过纳米脂质体递送，编辑的miR-379-5P模拟物显著抑制了肿瘤的生长和延长了小鼠的生存时间。我们的研究表明了RNA编辑在癌症进展过程中使miRNA功能多样化的作用，并强调了编辑后的miRNAs作为一类新的癌症治疗药物的翻译潜力。
Both miRNAs and A-to-I RNA editing, a widespread nucleotide modification mechanism, have recently emerged as key players in cancer pathophysiology. However, the functional impact of RNA editing of miRNAs in cancer remains largely unexplored. Here, we focused on an ADAR2-catalyzed RNA editing site within the miR-379-5p seed region. This site was under-edited in tumors relative to normal tissues, with a high editing level being correlated with better patient survival times across cancer types. We demonstrated that in contrast to wild-type miRNA, edited miR-379-5p inhibited cell proliferation and promoted apoptosis in diverse tumor contexts in vitro, which was due to the ability of edited but not wild-type miR-379-5p to target CD97. Importantly, through nanoliposomal delivery, edited miR-379-5p mimics significantly inhibited tumor growth and extended survival of mice. Our study indicates a role of RNA editing in diversifying miRNA function during cancer progression and highlights the translational potential of edited miRNAs as a new class of cancer therapeutics.