RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
合成短 mRNA 通过先天-适应性免疫预防转移
英文原题：Synthetic short mRNA prevents metastasis via innate-adaptive immunity.
查看英文原题
Synthetic short mRNA prevents metastasis via innate-adaptive immunity.
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中文摘要
尽管大多数癌症死亡由转移引起，但目前尚无有效的治疗方法。本研究描述了一种短合成 mRNA（s-mRNA）的疗效，该 mRNA 依据荷瘤小鼠转移前肺中发现的非囊泡细胞外 IL1β-mRNA 序列设计。给予 s-mRNA 通过诱导固有免疫和适应性免疫系统抑制小鼠肺转移。s-mRNA 与 ZC3H12D 结合，ZC3H12D 是NK 细胞和细胞毒性 T 淋巴细胞上的一种 RNA 结合蛋白。ZC3H12D-s-mRNA 复合物转位至细胞核，不参与翻译。该过程诱导癌细胞的细胞溶解活性和细胞死亡，而不诱导细胞因子风暴，免疫细胞保留其抗肿瘤活性。尽管癌症患者中细胞毒性淋巴细胞的抗肿瘤活性随疾病进展而下降，但 s-mRNA 可诱导结肠癌患者的NK 细胞和细胞毒性 T 淋巴细胞持续高杀伤能力。因此，s-mRNA 可能成为预防转移的突破性解决方案。
展开英文摘要原文
Although most cancer deaths are caused by metastasis, there are no effective therapeutic approaches.
This study describes the efficacy of a short synthetic mRNA (s-mRNA) designed by the sequence of non-vesicular extracellular IL1β-mRNA found in the pre-metastatic lung of tumor-bearing mice. The administration of s-mRNA inhibits murine lung metastasis by inducing the innate and adaptive immune systems. s-mRNA binds to ZC3H12D, an RNA-binding protein on natural killer cells and cytotoxic T lymphocytes.
The ZC3H12D-s-mRNA complex translocated to the nucleus without being involved in translation. This process induces cytolytic activity and cell death in cancer cells without inducing a cytokine storm, and immune cells retain their antitumor activity. Although the antitumor activity of cytotoxic lymphocytes declines as the disease progresses in cancer patients, s-mRNA induces sustained high killing capacities of natural killer cells and cytotoxic T lymphocytes from colon cancer patients.
Therefore, s-mRNA could be a breakthrough solution to prevent metastasis.
论文信息
- 作者
- Hayashi H、Seki S、Tomita T、Kato M、Ashihara N、Chano T、Sanjo H、Kawade M
- 第一作者单位
- Department of Biochemistry and Molecular Biology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, Japan.Japan
- 通讯作者单位
- Department of Biochemistry and Molecular Biology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, Japan. hira@shinshu-u.ac.jp.Japan
- 期刊
- Nature communications2025 Feb 25
- 原文标识
- PubMed 40000682 · DOI 10.1038/s41467-025-57123-y
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