高转移潜能的结直肠癌细胞通过传递外泌体 miR-20a-3p 来调节 NF1/MAPK 通路从而促进转移。

Colorectal cancer cells with high metastatic potential drive metastasis by transmitting exosomal miR-20a-3p through modulating NF1/MAPK pathway.

机构信息

Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China.

Gastrointestinal Surgical Institute, Nanchang University, Nanchang 330006, Jiangxi, China.

出版信息

Carcinogenesis. 2024 Oct 10;45(10):773-785. doi: 10.1093/carcin/bgae036.

DOI:10.1093/carcin/bgae036

PMID:38829328

Abstract

Cancer cells exhibit heterogeneous metastatic potential, and high metastatic (HM) subclones can enhance the metastatic potential of low metastatic subclones by transmitting some factors. Exosomal miRNAs play a pivotal role in the crosstalk of heterogeneous metastatic subclones. This study discovered that miR-20a-3p was upregulated in colorectal adenocarcinoma (CRA), correlated with metastasis, and potentially served as a prognostic indicator for CRA. miR-20a-3p could promote the proliferation, migration, and invasion of CRA cells. Interestingly, HM CRA cells could promote malignant phenotypes of low metastatic CRA cells by transmitting exosomal miR-20a-3p. Mechanically, miR-20a-3p could inhibit neurofibromin 1(NF1), thereby activate the rat sarcoma viral oncogene (RAS)-mediated mitogen-activated protein kinases (MAPK) signaling pathway to drive the metastasis of CRA. In summary, our study provided evidence that colorectal cancer cells with HM potential drive metastasis by transmitting exosomal miR-20a-3p through modulating the NF1/MAPK pathway.

摘要

癌细胞表现出异质性的转移潜能，高转移性（HM）亚克隆可以通过传递某些因子来增强低转移性亚克隆的转移潜能。外泌体 miRNAs 在异质性转移性亚克隆的串扰中发挥关键作用。本研究发现，miR-20a-3p 在结直肠腺癌（CRA）中上调，与转移相关，并可能作为 CRA 的预后指标。miR-20a-3p 可促进 CRA 细胞的增殖、迁移和侵袭。有趣的是，HM CRA 细胞可以通过传递外泌体 miR-20a-3p 促进低转移性 CRA 细胞的恶性表型。在机制上，miR-20a-3p 可以抑制神经纤维瘤 1（NF1），从而激活大鼠肉瘤病毒癌基因（RAS）介导的丝裂原激活蛋白激酶（MAPK）信号通路，驱动 CRA 的转移。总之，我们的研究提供了证据，表明具有 HM 潜力的结直肠癌细胞通过传递外泌体 miR-20a-3p 来调节 NF1/MAPK 通路，从而促进转移。