NIRF is frequently upregulated in colorectal cancer and its oncogenicity can be suppressed by let-7a microRNA

Np95 ICBP90 RING finger (NIRF) is essential for the regulation of cell proliferation and has been implicated in tumorigenesis. However, the role of NIRF in colorectal cancer (CRC) remains unclear. In this study, we demonstrated that NIRF expression was aberrantly increased in CRC tissues and associated with poor overall survival. Bioinformatics analysis indicated that NIRF was a putative target of the microRNA let-7a, which was confirmed by luciferase reporter assay. We then demonstrated in vitro that enforced expression of let-7a, or knockdown of NIRF, led to reduced CRC cell proliferation due to cell cycle arrest at the G0/G1 phase and reduced cell migration. Finally, an in vivo tumorigenicity assay in nude mice showed that synthetic let-7a suppressed NIRF expression and reduced tumor growth. Taken together, our results provide new evidence that NIRF has an oncogenic role in CRC. This opens up the possibility of targeting NIRF and let-7a for CRC therapy. (C) 2011 Elsevier Ireland Ltd. All rights reserved.