MicroRNA-217 functions as a prognosis predictor and inhibits colorectal cancer cell proliferation and invasion via an AEG-1 dependent mechanism

Background: Recent studies have indicated the possible function of miR-217 in tumorigenesis. However, the roles of miR-217 in colorectal cancer (CRC) are still largely unknown. Methods: We examined the expression of miR-217 and AEG-1 in 50 CRC tissues and the corresponding noncancerous tissues by qRT-PCR. The clinical significance of miR-217 was analyzed. CRC cell lines with miR-217 upregulation and AEG-1 silencing were established and the effects on tumor growth in vitro and in vivo were assessed. Dual-luciferase reporter gene assays were also performed to investigate the interaction between miR-217 and AEG-1. Results: Our data demonstrated that miR-217 was significantly downregulated in 50 pairs of colorectal cancer tissues. MiR-217 expression levels were closely correlated with tumor differentiation. Moreover, decreased miR-217 expression was also associated with shorter overall survival of CRC patients. MiR-217 overexpression significantly inhibited proliferation, colony formation and invasiveness of CRC cells by promoting apoptosis and G0/G1 phase arrest. Interestingly, ectopic miR-217 expression decreased AEG-1 expression and repressed luciferase reporter activity associated with the AEG-1 3'-untranslated region (UTR). AEG-1 silencing resulted in similar biological behavior changes to those associated with miR-217 overexpression. Finally, in a nude mouse xenografted tumor model, miR-217 overexpression significantly suppressed CRC cell growth. Conclusions: Our findings suggest that miR-217 has considerable value as a prognostic marker and potential therapeutic target in CRC.National Natural Science Foundation of China [81372290, 81372291]; Peking University People's Hospital Fund [RDB 2013-15]SCI(E)PubMedARTICLEshenlong1977@163.com; yeyingjiang@pkuph.edu.cn; shanwang60@sina.com4371