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Down‐regulation of KIAA1199/CEMIP by miR‐216a suppresses tumor invasion and metastasis in colorectal cancer
Authors:Qiong Shen  Qing Lv  Min Jin  Hong Ma  Xiu Nie  Xiumei Zheng  Shaoyi Huang  Pengfei Zhou  Gang Wu  Tao Zhang
Affiliation:1. Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China;2. Department of Gastroenterology Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China;3. Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China;4. Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China;5. Wuhan YZY Medical Science & Technology Co, Ltd, Wuhan, People's Republic of China
Abstract:Colorectal cancer is one of the major causes of death from cancer. Metastasis is the leading cause of treatment failure, in which cancer stem cells and circulating tumor cells play crucial roles. Identifying the involved metastatic biomarkers and clarifying the regulation mechanisms are of great importance for targeting tumor metastasis. In the current research, we discovered that KIAA1199, a cell‐migration inducing protein, showed higher expression in CD44+ cancer cells from metastatic compared with the paired primary tissues, and was upregulated in colorectal cancer and positively correlated with numbers and mesenchymal phenotype of circulating tumor cells, and predicted shorter progress‐free survival. Moreover, we indicated that down‐regulation of KIAA1199 suppressed migration and invasion of colorectal cancer cells in vitro, and inhibited metastasis in vivo. Furthermore, we demonstrated that KIAA1199 was one of the direct and functional targets of miR‐216a, and miR‐216a overexpression led to decreased migration and invasion of colorectal cancer cells in vitro, and inhibited metastasis in vivo. Collectively, KIAA1199 plays a critical role in maintaining an aggressive phenotype of tumor cells, and suppression of KIAA1199‐related motilities of tumor cells contributes to reduced tumor metastasis in colorectal cancer.
Keywords:colorectal cancer  metastasis  cancer stem cells  circulating tumor cells  KIAA1199  miR‐216a
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