Department of Gastrointestinal Surgery, Liuzhou People's Hospital, Liuzhou 545006, Guangxi, China.
Exp Biol Med (Maywood). 2023 Sep;248(18):1527-1536. doi: 10.1177/15353702231199070. Epub 2023 Oct 14.
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.
结直肠癌(CRC)通常在晚期诊断,死亡率较高。三结构域含 29 个(TRIM29)是包括 CRC 在内的多种恶性肿瘤的癌基因。然而,TRIM29 的分子机制在很大程度上尚不清楚。在这项研究中,我们研究了 TRIM29 的生物学功能及其潜在机制。使用生物信息学分析预测 TRIM29 和 Enhancer of Zeste Homolog 2(EZH2)的表达,并使用定量实时聚合酶链反应(PCR)和免疫组织化学检测进行测量。使用细胞计数试剂盒-8、EdU 和 Transwell 测定、划痕试验和流式细胞术分析 TRIM29 的生物学功能。使用蛋白质免疫沉淀评估 TRIM29 和 EZH2 之间的相互作用。用环己酰亚胺处理来评估 EZH2 的稳定性。我们的结果表明,CRC 中 TRIM29 水平上调。过表达 TRIM29 促进 CRC 细胞增殖、迁移和抑制凋亡。当 TRIM29 被沉默时则得到相反的结果。TRIM29 与 EZH2 机械相互作用并增强 EZH2 的蛋白稳定性。耗尽 EZH2 逆转了 TRIM29 的生物学行为。此外,下调 TRIM29 抑制肿瘤生长并改善组织病理学预后。总之,EZH2 与沉默的 TRIM29 相互作用以抑制其稳定性,从而抑制 CRC 中的细胞增殖、迁移和肿瘤生长,并促进凋亡。我们的研究结果表明,TRIM29 是 CRC 治疗的一个有前途的靶点。