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Exosome-delivered miR-221/222 exacerbates tumor liver metastasis by targeting SPINT1 in colorectal cancer

Cancer Sci. 2021-07; 
Fei Tian, Peiyun Wang, Dan Lin, Jiajia Dai, Qibing Liu, Yu Guan, Yang Zhan, Yichen Yang, Wenpeng Wang, Jiefu Wang, Jia Liu, Lei Zheng, Yan Zhuang, Jun Hu, Junfeng Wang, Dalu Kong, Kegan Zhu
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摘要

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... More

关键词

colorectal cancer, exosome, liver metastasis, miR-221, miR-222