外泌体来源的 M2 巨噬细胞 miRNA-21-5p 通过 PTEN/Akt 信号通路促进肾细胞癌肿瘤细胞侵袭。

The miRNA-21-5p Payload in Exosomes from M2 Macrophages Drives Tumor Cell Aggression via PTEN/Akt Signaling in Renal Cell Carcinoma.

机构信息

Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.

Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, CA 90095, USA.

出版信息

Int J Mol Sci. 2022 Mar 10;23(6):3005. doi: 10.3390/ijms23063005.

DOI:10.3390/ijms23063005

PMID:35328425

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8949275/

Abstract

M2 macrophages in the tumor microenvironment are important drivers of cancer metastasis. Exosomes play a critical role in the crosstalk between different cells by delivering microRNAs or other cargos. Whether exosomes derived from pro-tumorigenic M2 macrophages (M2-Exos) could modulate the metastatic behavior of renal cell carcinoma (RCC) is unclear. This study found that M2-Exos promotes migration and invasion in RCC cells. Inhibiting miR-21-5p in M2-Exos significantly reversed their pro-metastatic effects on RCC cells in vitro and in the avian embryo chorioallantoic membrane in vivo tumor model. We further found that the pro-metastatic mechanism of miR-21-5p in M2-Exos is by targeting PTEN-3'UTR to regulate PTEN/Akt signaling. Taken together, our results demonstrate that M2-Exos carries miR-21-5p promote metastatic features of RCC cells through PTEN/Akt signaling. Reversing this could serve as a novel approach to control RCC metastasis.

摘要

肿瘤微环境中的 M2 巨噬细胞是癌症转移的重要驱动因素。外泌体通过传递 microRNAs 或其他 cargo 在不同细胞之间的串扰中发挥关键作用。源自促肿瘤发生的 M2 巨噬细胞（M2-Exos）的外泌体是否能够调节肾细胞癌（RCC）的转移行为尚不清楚。本研究发现 M2-Exos 可促进 RCC 细胞的迁移和侵袭。在体外和鸡胚尿囊膜体内肿瘤模型中，抑制 M2-Exos 中的 miR-21-5p 可显著逆转其对 RCC 细胞的促转移作用。我们进一步发现，M2-Exos 中 miR-21-5p 的促转移机制是通过靶向 PTEN-3'UTR 来调节 PTEN/Akt 信号通路。总之，我们的研究结果表明，M2-Exos 通过携带 miR-21-5p 通过 PTEN/Akt 信号通路促进 RCC 细胞的转移特征。逆转这种情况可能成为控制 RCC 转移的一种新方法。