Abstract
Interleukin enhancer binding factor 2 (ILF2) has been confirmed to drive the progression and proliferation of multiple malignancies, but the expression and function of ILF2 in colorectal cancer (CRC) remain to be elucidated. In this study, the expression of ILF2 in CRC tissues was evaluated by the public tumor databases, quantitative reverse transcription PCR (qRT-PCR) and tissue array analyses. ILF2 was found to be elevated in CRC, and was predicted to serve as a negative index for patients. Subsequently, cell proliferation was detected by Cell Counting Kit-8 (CCK-8) assay and colony formation, and tumor growth was evaluated by establishing xenografted mouse models. Our results showed that knockout of ILF2 markedly inhibited cell proliferation and tumor growth of CRC. Moreover, we found ILF2 was ubiquitinated, and further co-immunoprecipitation (Co-IP) coupled with liquid chromatography-tandem mass spectrometry analysis indicated that ILF2 may be a novel substrate of the deubiquitinating enzyme ubiquitin specific peptidase 5 (USP5). Further reciprocal Co-IP assays confirmed that ILF2 interacted with USP5. Enforced expression of USP5 reduced ubiquitinated ILF2 and increased ILF2 level, whereas catalytic inactive USP5 did not. While USP5 inhibitor WP1130 downregulated ILF2 and inhibited CRC cell growth, the effects were markedly abolished by ILF2 overexpression. These data demonstrate that the USP5/ILF2 axis mediates the tumorigenesis of CRC, which highlights the USP5/ILF2 axis as a promising therapeutic target for CRC treatment.