TRIM29 promotes the progression of colorectal cancer by suppressing EZH2 degradation.

Abstract

Colorectal cancer (CRC) is commonly diagnosed at the advanced stage and has a high mortality rate. Tripartite Motif Containing 29 (TRIM29) is an oncogene in numerous malignancies including CRC. However, the molecular mechanism of TRIM29 is largely unknown. In this study, we investigated the biological functions of TRIM29 and the underlying mechanisms. The expression of TRIM29 and Enhancer of Zeste Homolog 2 (EZH2) was predicted using the bioinformatic analysis and measured using a quantitative real-time polymerase chain reaction (PCR) and immunohistochemical assay. The biological functions of TRIM29 were analyzed using a cell counting kit-8, EdU and transwell assays, scratch test, and flow cytometry. The interaction between TRIM29 and EZH2 was assessed using protein immunoprecipitation. The stability of EZH2 was evaluated by treating it with cycloheximide. Our results indicated that TRIM29 levels were upregulated in CRC. Overexpression of TRIM29 promoted CRC cell proliferation and migration and suppressed apoptosis. The opposite result was obtained when TRIM29 was silenced. TRIM29 interacted with EZH2 mechanically and enhanced the protein stability of EZH2. Depletion of EZH2 reversed the effects of TRIM29, regarding its biological behaviors. Moreover, downregulation of TRIM29 inhibited tumor growth and improved the histopathological prognosis. In conclusion, EZH2 interacted with silenced TRIM29 to suppress its stability, thereby inhibiting cell proliferation, migration, and tumor growth, and promoting apoptosis in CRC. Our findings suggested that TRIM29 is a promising target for CRC therapy.