TRIM47 Promotes the Development of Glioma by Ubiquitination and Degradation of FOXO1
Huaming Wei, Chonglan Ding, Huanxia Zhuang, Wei-Li Hu
Abstract
Objective: To investigate the effect of TRIM47 on glioma cells and further explore its underlying molecular mechanisms. Methods: Mouse xenograft model was used in this study. The mRNA expression of TRIM47 was detected by qRT-PCR. The cell viability and proliferation activity was detected by MTT assay and colony formation assay. The migration and invasion of glioma cells were determined by Transwell assay. The protein levels of TRIM47 , FOXO1, CyclinD1, C-myc, MMP-2 and TIMP-1 were assessed by Western-blotting. The interaction between TRIM47 and FOXO1 was measured by Co-immunoprecipitation (Co-IP) assay. Results: In glioma tissues and cells, TRIM47 was significantly up-regulated. Silencing the expression of TRIM47 inhibited the cell viability and proliferation of cells A172 and U251, as well as their ability to invade and migrate. Among them, the expression levels of C-myc and CyclinD1 also decreased, and MMP-2 was down-regulated and TIMP-1 was up-regulated. Similarly, in vivo model, tumor volume and weight also decreased after TRIM47 knockout. Further research showed that TRIM47 inhibited FOXO1 expression by ubiquitination and degradation of FOXO1 , thereby promoting glioma growth and progression. Conclusion: In our study, we confirmed functional role of the TRIM47-FOXO1 axis in the progression of gliomas and provided a potential target for glioma treatment. Keywords: glioma, tripartite motif 47, forkhead box O1, proliferation, migration, invasion