TRIM47 Is Up-regulated In Colorectal Cancer,Promoting Tumorigenesis By Ubiquitination And Degradation Of SMAD4

Tripartite motif 47(TRIM47),a member of the TRIM family proteins,plays the role of E3 ubiquitin ligase in many types of cancers.However,the pathologic role and the mechanism of TRIM47 have not been revealed in colorectal cancer.Here we measure the levels of TRIM47 m RNA and protein in human colorectal cancer and paired normal tissues.TRIM47 is overexpressed in colorectal cancer,and correlated with disease progression as well as poor prognosis.TRIM47 is knocked down and overexpressed in colorectal cancer cells,and the effects on cell proliferation,migration and growth of xenograft tumors in nude mice are assessed.The results show that TRIM47 promotes CRC proliferation and metastasis in vitro and in vivo as an oncogene.Mechanistically,TRIM47 interacts physically with SMAD4,increasing its ubiquitination and degradation.Loss of SMAD4 leads to up-regulation of CCL15 expression and causes growth and invasion in human CRC cells through the CCL15-CCR1 signaling.Moreover,TRIM47 overexpression plays a role in CRC chemoresistance in response to 5-Fu therapy.Thus,we could draw a conclusion that our study demonstrates a functional role of the TRIM47-SMAD4-CCL15 axis in CRC progression and suggests a potential target for CRC early diagnosis and therapy.