外泌体介导的 lncRNAHCG18 转移促进胃癌中 M2 巨噬细胞的极化。
Exosome-mediated transfer of lncRNA HCG18 promotes M2 macrophage polarization in gastric cancer.
机构信息
Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China.
Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China.
出版信息
Mol Immunol. 2021 Dec;140:196-205. doi: 10.1016/j.molimm.2021.10.011. Epub 2021 Oct 29.
BACKGROUND
Gastric cancer (GC) derived exosomes (Exos) aggravate GC development by facilitating M2 macrophage polarization and long non-coding RNA (lncRNA) HCG18 was highly expressed in GC. This study aimed to investigate whether the exosomal lncRNA HCG18 regulated the M2 macrophage polarization in GC and the possible mechanism.
METHODS
The isolated GC cells (GCCs)-Exos were identified using transmission electron microscopy, Nanoparticle Tracking Analysis and Western blot. The GCCs-Exos function was verified by enzyme-linked immunosorbent assay and flow cytometry. Meanwhile, the exosomal lncRNA HCG18 function was determined using thein vitro assays. Furthermore, the underlying mechanism of the exosomal lncRNA HCG18 that regulated M2 macrophage polarization in GC was investigated using dual-luciferase reporter gene assay and RNA pull-down.
RESULTS
After the validation of GCCs-Exos, the GCCs-Exos facilitated the M2 macrophage polarization. The in vitro assays confirmed that the exosomal lncRNA HCG18 positively regulated the M2 macrophage polarization. Mechanistically, lncRNA HCG18 bound to miR-875-3p, miR-875-3p bound to KLF4. Furthermore, GCCs-exosomal lncRNA HCG18 elevated the KLF4 expression by decreasing miR-875-3p in macrophages to facilitate M2 macrophage polarization, thus alleviating GC. The in vivo assays clarified that the GCCs-exosomal lncRNA HCG18 restrained the tumor growth of GC induced by M2 macrophages.
CONCLUSION
GCCs-exosomal lncRNA HCG18 elevated KLF4 expression by decreasing miR-875-3p in macrophages to facilitate the M2 macrophage polarization.
背景
胃癌（GC）衍生的外泌体（Exos）通过促进 M2 巨噬细胞极化加重 GC 的发展，HCG18 长链非编码 RNA（lncRNA）在 GC 中高表达。本研究旨在探讨外泌体 lncRNA HCG18 是否调节 GC 中 M2 巨噬细胞极化及其可能的机制。
方法
通过透射电子显微镜、纳米颗粒跟踪分析和 Western blot 鉴定分离的 GC 细胞（GCCs）-Exos。通过酶联免疫吸附测定和流式细胞术验证 GCCs-Exos 的功能。同时，通过体外实验确定外泌体 lncRNA HCG18 的功能。此外，通过双荧光素酶报告基因检测和 RNA 下拉实验研究外泌体 lncRNA HCG18 调节 GC 中 M2 巨噬细胞极化的潜在机制。
结果
在验证了 GCCs-Exos 后，GCCs-Exos 促进了 M2 巨噬细胞极化。体外实验证实，外泌体 lncRNA HCG18 正向调节 M2 巨噬细胞极化。机制上，lncRNA HCG18 与 miR-875-3p 结合，miR-875-3p 与 KLF4 结合。此外，GCCs-exosomal lncRNA HCG18 通过降低巨噬细胞中的 miR-875-3p 来升高 KLF4 表达，从而促进 M2 巨噬细胞极化，从而缓解 GC。体内实验表明，GCCs-exosomal lncRNA HCG18 通过降低巨噬细胞中的 miR-875-3p 来抑制由 M2 巨噬细胞诱导的 GC 肿瘤生长。
结论
GCCs-exosomal lncRNA HCG18 通过降低巨噬细胞中的 miR-875-3p 来升高 KLF4 表达，从而促进 M2 巨噬细胞极化。
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