Exosome-delivered miR-221/222 exacerbates tumor liver metastasis by targeting SPINT1 in colorectal cancer |
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| Authors: | 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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| Affiliation: | 1. Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin, China;2. Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China;3. Hainan Provincial Research Center for Innovative Drugs Clinical Evaluation, The First Affiliated Hospital of Hainan Medical University, Haikou, China;4. Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China |
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| Abstract: | ![]()
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. |
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| Keywords: | colorectal cancer exosome liver metastasis miR-221 miR-222 |
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