TRIM47 Promotes the Development of Glioma by Ubiquitination and Degradation of FOXO1

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 upregulated. 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.

Featured interactome of homocysteine-inducible endoplasmic reticulum protein uncovers novel binding partners in response to ER stress

“…The posttranslational modifications (PTMs) is pivotal in the functional proteome by affecting the activity, localization, and interaction with other cellular molecules of proteins [43] . TRIM47 is an oncogene and involved in promoting cancer cell proliferation by ubiquitination of substrates, including p53, fructose-1,6-bisphosphatase 1 (FBP1), forkhead box O1 (FOXO1) and SMAD4 [44] , [45] , [46] , [47] . In addition, TRIM47 also plays a critical function in innate immunity through the increase of the K48-linked ubiquitination of NF90 and K63-linked ubiquitination of TNF receptor-associated factor 2 (TRAF2) [35] , [48] .…”

FoxO1 promotes ovarian cancer by increasing transcription and METTL14‐mediated m6A modification of SMC4

“…Functional experiments further demonstrated FoxO1 in promoting the proliferation, migration, and invasion of OC in vitro and in vivo, suggesting that FoxO1 can be used as a useful independent prognostic marker in OC. As is well known, various post‐translational modifications of FoxO1, such as phosphorylation, acetylation and ubiquitination, are closely related to tumorigenesis 46–48 . Further exploration of the modification level of FoxO1 protein in OC could better explain the mechanism of FoxO1.…”

“…As is well known, various post‐translational modifications of FoxO1, such as phosphorylation, acetylation and ubiquitination, are closely related to tumorigenesis. 46 , 47 , 48 Further exploration of the modification level of FoxO1 protein in OC could better explain the mechanism of FoxO1.…”

A Famous Chinese Medicine Formula: Yinhuo Decoction Antagonizes the Damage of Corticosterone to PC12 Cells and Improves Depression by Regulating the SIRT1/PGC-1α Pathway

“…Protein expression levels were semiquantified using ImageJ software (version 1.8.0; National Institutes of Health). [20], the brain tissues were formalin-fixed and paraffin-embedded, sliced into 4 μmthick sections. Graded ethanol was used to rehydrate the sections after deparaffinization in xylene at room temperature.…”