Tripartite motif-containing 54 promotes gastric cancer progression by upregulating K63-linked ubiquitination of filamin C.

Abstract

Tripartite motif (TRIM) proteins have been proved to contribute to cancer progression, while whether tripartite motif-containing 54 (TRIM54) could functionally influence gastric cancer (GC) progression remains elusive. The expression level of TRIM54 and filamin C (FLNC) in GC was determined by Western blot and online database. Cell Counting Kit-8 (CCK-8) assay, colony formation assay and Ethylenediurea (EdU) staining were performed to explore the effects of TRIM54 on GC cell proliferation. Transwell assay and wound healing assay were applied to detect the influence of TRIM54 on GC cell migration and invasion. Bioinformatics analysis and Co-immunoprecipitation assay (Co-Ip), Ubiquitination assay and Half-life assay were involved to explore the regulatory mechanism of TRIM54 on FLNC. TRIM54 was upregulated in GC tissues and cells, and a higher expression level of TRIM54 indicated a shorter overall survival of GC patients. The overexpression of TRIM54 significantly enhanced proliferation, migration, and invasion of GC cells, and inhibition of TRIM54 expression exerted reverse effects on GC cells. Mechanistically, TRIM54 was determined as a post-translational mediator of FLNC, and TRIM54 was co-immunoprecipitated with FLNC and degraded its protein level via K63-linked ubiquitination of FLNC. Notably, FLNC efficiently inhibited GC progression by TRIM54 overexpression. Collectively, our findings suggested that the TRIM54/FLNC axis could be considered as a potential prognostic biomarker for GC.