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
ELFN1-AS1 通过促进 GCN5 与 SND1 结合促进 GDF15 介导的结直肠癌对 NK 细胞的免疫逃逸
英文原题：ELFN1-AS1 promotes GDF15-mediated immune escape of colorectal cancer from NK cells by facilitating GCN5 and SND1 association.
查看英文原题
ELFN1-AS1 promotes GDF15-mediated immune escape of colorectal cancer from NK cells by facilitating GCN5 and SND1 association.
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中文摘要
结直肠癌（CRC）细胞逃逸自然杀伤（NK）细胞免疫监视的能力导致抗肿瘤治疗失败。长链非编码 RNA（lncRNA）ELFN1-AS1 在多种肿瘤中异常表达，提示其在癌症发展中作为癌基因发挥作用。
然而，ELFN1-AS1 是否调控 CRC 中的免疫监视尚不清楚。在此，我们确定 ELFN1-AS1 在体外和体内增强了 CRC 细胞逃逸 NK 细胞监视的能力。
此外，我们证实 CRC 细胞中的 ELFN1-AS1 通过 GDF15/JNK 通路下调 NKG2D 和 GZMB 来减弱 NK 细胞的活性。
进一步，机制研究表明 ELFN1-AS1 增强了 GCN5 与 SND1 蛋白之间的相互作用，这影响了 GDF15 启动子处 H3k9ac 的富集，从而刺激 CRC 细胞中 GDF15 的产生。
综上所述，我们的发现表明 CRC 细胞中的 ELFN1-AS1 抑制 NK 细胞毒性，ELFN1-AS1 是 CRC 的潜在治疗靶点。
展开英文摘要原文
The ability of colorectal cancer (CRC) cells to escape from natural killer (NK) cell immune surveillance leads to anti-tumor treatment failure. The long non-coding RNA (lncRNA) ELFN1-AS1 is aberrantly expressed in multiple tumors suggesting a role as an oncogene in cancer development.
However, whether ELFN1-AS1 regulates immune surveillance in CRC is unclear.
Here, we determined that ELFN1-AS1 enhanced the ability of CRC cells to escape from NK cell surveillance in vitro and in vivo.
In addition, we confirmed that ELFN1-AS1 in CRC cells attenuated the activity of NK cell by down-regulating NKG2D and GZMB via the GDF15/JNK pathway.
Furthermore, mechanistic investigations demonstrated that ELFN1-AS1 enhanced the interaction between the GCN5 and SND1 protein and this influenced H3k9ac enrichment at the GDF15 promotor to stimulate GDF15 production in CRC cells. Taken together, our findings indicate that ELFN1-AS1 in CRC cells suppresses NK cell cytotoxicity and ELFN1-AS1 is a potential therapeutic target for CRC.
论文信息
- 作者
- Han B、He J、Chen Q、Yuan M、Zeng X、Li Y、Zeng Y、He M
- 第一作者单位
- GCP Center/Institute of Drug Clinical Trials, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.China
- 通讯作者单位
- GCP Center/Institute of Drug Clinical Trials, Affiliated Hospital of North Sichuan Medical College, Nanchong, China. mdylx@163.com.China
- 期刊
- Discover oncology2023 May 6
- 原文标识
- PubMed 37147528 · DOI 10.1007/s12672-023-00675-6
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