General Surgery Department, Shanghai Baoshan Hospital of Integrated Traditional Chinese Medicine and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201999, China.
Department of Gastrointestinal Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
J Cell Mol Med. 2018 Oct;22(10):5020-5028. doi: 10.1111/jcmm.13784. Epub 2018 Aug 5.
The tripartite motif (TRIM) family comprises more than 70 members involved in the regulation of many cellular pathways. TRIM32 acts as an E3 ubiquitin ligase and has been reported to participate in many human cancers. Here, we aimed to investigate the role of TRIM32 in gastric cancer (GC) and the clinical implications. High expression of TRIM32 was observed in GC tissues and cell lines, and was significantly associated with poor prognosis. Knockdown TRIM32 expression remarkably suppressed the proliferation, migration, and invasion of GC cells in vitro and tumour growth in vivo, whereas overexpression of TRIM32 yielded the opposite results. Western blotting and quantitative reverse-transcription PCR (qRT-PCR) analyses revealed that up-regulation of TRIM32 significantly enhanced expression of β-catenin protein and of its downstream targets TCF1, cyclin D1, Axin2 and MMP7 mRNAs. Moreover, we found that the mechanism behind the TRIM32-promoted GC progression was related to the β-catenin signalling pathway. Collectively, these data suggest that TRIM32 promotes GC cell proliferation, migration, and invasion by activating the β-catenin signalling pathway.
三结构域蛋白(TRIM)家族由 70 多个成员组成,参与许多细胞途径的调节。TRIM32 作为 E3 泛素连接酶,据报道参与了许多人类癌症。在这里,我们旨在研究 TRIM32 在胃癌(GC)中的作用及其临床意义。TRIM32 在 GC 组织和细胞系中的表达较高,与预后不良显著相关。TRIM32 表达的敲低显著抑制了 GC 细胞在体外的增殖、迁移和侵袭以及体内的肿瘤生长,而 TRIM32 的过表达则产生了相反的结果。Western blot 和定量逆转录聚合酶链反应(qRT-PCR)分析显示,TRIM32 的上调显著增强了 β-catenin 蛋白及其下游靶标 TCF1、cyclin D1、Axin2 和 MMP7 mRNA 的表达。此外,我们发现 TRIM32 促进 GC 进展的机制与 β-catenin 信号通路有关。总之,这些数据表明 TRIM32 通过激活 β-catenin 信号通路促进 GC 细胞的增殖、迁移和侵袭。