Open AccessExosome‐delivered miR‐221/222 exacerbates tumor liver metastasis by targeting SPINT1 in colorectal cancer
Author(s) -
Tian Fei,
Wang Peiyun,
Lin Dan,
Dai Jiajia,
Liu Qibing,
Guan Yu,
Zhan Yang,
Yang Yichen,
Wang Wenpeng,
Wang Jiefu,
Liu Jia,
Zheng Lei,
Zhuang Yan,
Hu Jun,
Wang Junfeng,
Kong Dalu,
Zhu Kegan
Publication year - 2021
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.15028
Subject(s) - microvesicles , downregulation and upregulation , exosome , colorectal cancer , metastasis , microrna , cancer research , hepatocyte growth factor , tumor progression , medicine , cancer , biology , gene , biochemistry , receptor
MicroRNAs (miRNAs) are involved in the progression of many cancers through largely unelucidated mechanisms. The results of our present study identified a gene cluster, miR‐221/222, that is constitutively upregulated in serum exosome samples of patients with colorectal carcinoma (CRC) with liver metastasis (LM); this upregulation predicts a poor overall survival rate. Using an in vitro cell coculture model, we demonstrated that CRC exosomes harboring miR‐221/222 activate liver hepatocyte growth factor (HGF) by suppressing SPINT1 expression. Importantly, miR‐221/222 plays a key role in forming a favorable premetastatic niche (PMN) that leads to the aggressive nature of CRC, which was further shown through in vivo studies. Overall, our results show that exosomal miR‐221/222 promotes CRC progression and may serve as a novel prognostic marker and therapeutic target for CRC with LM.