TRIM29 promotes the progression of colorectal cancer by suppressing EZH2 degradation
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Yuanjian Chen1, Jun Ma1, Mingming Zhang1
1Department of Gastrointestinal Surgery, Liuzhou People's Hospital, Liuzhou 545006, Guangxi, China.
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.
Insights
Tripartite Motif Containing 29 (TRIM29) promotes colorectal cancer (CRC) by enhancing Enhancer of Zeste Homolog 2 (EZH2) stability. Targeting TRIM29 may offer a new therapeutic strategy for CRC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Colorectal cancer (CRC) often presents at advanced stages, leading to high mortality rates.
- Tripartite Motif Containing 29 (TRIM29) is recognized as an oncogene in various cancers, including CRC, but its precise molecular mechanisms remain unclear.
Purpose of the Study:
- To elucidate the biological functions of TRIM29 in colorectal cancer.
- To investigate the molecular mechanisms underlying TRIM29's role in CRC progression.
- To explore the potential of TRIM29 as a therapeutic target for CRC.
Main Methods:
- Bioinformatic analysis, quantitative real-time PCR, and immunohistochemical assays were used to assess TRIM29 and EZH2 expression.
- Cell proliferation, migration, and apoptosis were evaluated using cell counting kit-8, EdU, transwell assays, scratch tests, and flow cytometry.
- Protein immunoprecipitation and cycloheximide treatment were employed to study the interaction and stability of TRIM29 and EZH2.
Main Results:
- TRIM29 expression was found to be upregulated in CRC tissues.
- Overexpression of TRIM29 enhanced CRC cell proliferation and migration while suppressing apoptosis; conversely, TRIM29 silencing had opposite effects.
- TRIM29 was shown to interact with and increase the protein stability of EZH2, and EZH2 depletion reversed TRIM29's pro-cancerous effects.
Conclusions:
- TRIM29 promotes colorectal cancer progression by enhancing EZH2 protein stability, thereby increasing cell proliferation and migration and inhibiting apoptosis.
- Downregulation of TRIM29 demonstrated potential in inhibiting tumor growth and improving histopathological prognosis in CRC.
- TRIM29 emerges as a significant oncogene in CRC and a promising therapeutic target.
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