2. Academic Validation
  3. Exosome-transmitted miR-29a induces colorectal cancer metastasis by destroying the vascular endothelial barrier

Exosome-transmitted miR-29a induces colorectal cancer metastasis by destroying the vascular endothelial barrier

  • Carcinogenesis. 2023 Mar 20;bgad013. doi: 10.1093/carcin/bgad013.
Keshu Liu 1 2,  Rongzhang Dou 1 2,  Chaogang Yang 1 2,  Ziyang Di 1 2,  Dongdong Shi 1 2,  Chunxiao Zhang 1 2,  Jialin Song 1 2,  Yan Fang 1 2,  Sihao Huang 1 2,  Zhenxian Xiang 1 2,  Weisong Zhang 1 2,  Shuyi Wang 1 2,  Bin Xiong 1 2
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, No.169 Donghu Road, Wuchang District, Wuhan, 430071, China.
  • 2 Hubei Key Laboratory of Tumor Biological Behaviors, No.169 Donghu Road, Wuchang District, Wuhan, 430071, China.
PMID: 36939367 DOI: 10.1093/carcin/bgad013
Abstract

Metastasis is the leading cause of colorectal Cancer treatment failure and mortality. Communication between endothelium and tumor cells in the tumor microenvironment is required for Cancer metastasis. Tumor-derived exosomes have been shown to increase vascular permeability by delivering MicroRNA (miRNA) to vascular endothelial cells, facilitating Cancer metastasis. The mechanism by which Epithelial mesenchymal transition (EMT) tumor cell-derived exosomes influence vascular permeability remains unknown. MicroRNA-29a (miR-29a) expression is up-regulated in colorectal Cancer (CRC)tissues, which is clinically significant in metastasis. Exosomal miR-29a secreted by EMT-CRC cells has been found to decrease the expression of Zonula occlusion 1 (ZO-1), Claudin-5, and Occludin via targeting Kruppel-like factor 4 (KLF4). In vitro co-culture investigations further revealed that EMT Cancer cells release exosomal miR-29a, which alters vascular endothelial permeability. Furthermore, exosomal miR-29a promoted liver metastases in CRC mice. Our findings demonstrate that EMT-CRC cells may transport exosomal miR-29a to endothelial cells in the tumor microenvironment (TME). As a result, increased vascular permeability promotes the development and metastasis of CRC. Exosomal miR-29a has the potential to be a predictive marker for tumor metastasis as well as a viable therapeutic target for CRC.

Keywords

EMT; colorectal cancer; exosomes; metastasis; miR-29a.

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