Tripartite motif containing 33 demonstrated anticancer effect by degrading c‑Myc: Limitation of glutamine metabolism and proliferation in endometrial carcinoma cells

Abstract

Tripartite motif containing 33 (TRIM33) has been reported to be involved in various tumor progression. However, its role in endometrial carcinoma (EC) remains to be elucidated. By mining the publicly available databases UALCAN and TIMER, low expression of TRIM33 was found in tumor tissues of EC patients. Clinically, downregulation of TRIM33 in EC tissues was positively correlated with the extensive muscle invasion and poor differentiation grade. In vitro , experiments performed on human HEC-1-A and AN3CA cells showed that overexpression of TRIM33 inhibited the proliferation, migration and invasion of EC cells, whereas TRIM33 knockdown resulted in the opposite results. Furthermore, upregulation of TRIM33 significantly inhibited the glutamine uptake and decreased the intracellular glutamate in EC cells, which is evidenced by the reduction of solute carrier family 1 member 5 and glutaminase. In vivo , TRIM33 also dramatically inhibited tumor growth and glutamine metabolism. Additionally, co-immunoprecipitation assay confirmed the interaction between TRIM33 and c-Myc. Overexpression of TRIM33 could reduce the protein stability of c-Myc by promoting its degradation. In addition, upregulation of c-Myc could reverse the effects of TRIM33 on EC cells. Together, the present study demonstrated that TRIM33 acted as a tumor suppressor in EC, which is manifested in its inhibition of glutamine metabolism and cell growth via promoting c-Myc protein degradation.