MicroRNA-375 suppresses human colorectal cancer metastasis by targeting Frizzled 8
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Lingling Xu1,*, Tao Wen2,*, Zhe Liu1, Feng Xu1, Lei Yang2, Jian Liu2, Guosheng Feng1, Guangyu An1
1Department of Oncology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China
2Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China
*These two authors contributed equally to this work
Guangyu An, email: firstname.lastname@example.org
Guosheng Feng, email: email@example.com
Keywords: colorectal cancer, microRNA-375, metastasis, FZD8
Received: December 20, 2015 Accepted: May 17, 2016 Published: June 3, 2016
microRNAs are aberrantly expressed during the development and progression of a variety of human cancers, including colorectal cancer (CRC). Of these microRNAs, microRNA-375 (miR-375) was previously observed to be downregulated in human colorectal cancer(CRC) plasma and tissues, but its functions are largely unknown. Here, we investigated the impact of miR-375 on CRC metastasis. Specifically, miR-375 expression was significantly decreased in human CRC tissues compared with their matched noncancerous tissues (NCTs), and low levels of miR-375 predicted tumor metastatic potential. The up-regulation of miR-375 suppressed colorectal cancer cell migration and invasion in vitro and reduced tumor metastases in murine models established by both orthotopic implantation and spleen injection. Furthermore, we identified Frizzled 8 (FZD8) as a direct target of miR-375 in CRC, and miR-375 negatively regulated Wnt/β-catenin signaling by suppressing FZD8. More importantly, FZD8 expression inversely correlated with overall survival in human CRC patients and is a likely independent predictor of survival. Therefore, we concluded that miR-375 functions as a tumor-suppressive microRNA by directly acting upon FZD8, which may serve as a new therapeutic target to inhibit tumor metastasis in CRC.
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