MicroRNA-375 suppresses human colorectal cancer metastasis by targeting Frizzled 8.
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.
Department of Oncology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
Lingling
L
Xu
Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
Tao
T
Wen
Department of Oncology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
Zhe
Z
Liu
Department of Oncology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
Feng
F
Xu
Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
Lei
L
Yang
Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
Jian
J
Liu
Department of Oncology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
Guosheng
G
Feng
Department of Oncology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
Guangyu
G
An
D000818:Animals; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D016896:Treatment Outcome; D015854:Up-Regulation; D014945:Wound Healing
C529739:Fzd8 protein, human; C540933:MIRN375 microRNA, human; D035683:MicroRNAs; D011956:Receptors, Cell Surface
FZD8; colorectal cancer; metastasis; microRNA-375