Yin Yan, Zhong Jun, Li Si-Wei, Li Jian-Zhe, Zhou Min, Chen Yin, Sang Yi, Liu Lijuan
Department of Pharmacy, Jiangxi Cancer Hospital, Nanchang, China.
Department of Radiotherapy, Jiangxi Cancer Hospital, Nanchang, China.
Oncotarget. 2016 Dec 27;7(52):86755-86765. doi: 10.18632/oncotarget.13550.
TRIM11 (tripartite motif-containing protein 11) is an E3 ubiquitin ligase recently identified as an oncogene in malignant glioma and lung cancer. In the present study, we report that expression of TRIM11 was increased in colon cancer (CC) tissue relative to paired normal tissues and that higher TRIM11 levels predicted poor overall survival (OS) and disease-free survival (DFS) in CC patients. Mechanistically, we showed that miR-24-3p downregulation contributes to TRIM11 upregulation in CC. We also demonstrated that TRIM11 overexpression promotes cell proliferation and colony formation and inhibits apoptosis in CC, while knocking down TRIM11 using CRISPR/Cas9-mediated genome editing inhibited cell proliferation and induced apoptosis. Silencing TRIM11 in vivo decreased tumor growth. These findings indicate that TRIM11 facilitates CC progression by promoting cell proliferation and inhibiting apoptosis and that the novel miR-24-3p/TRIM11 axis may be a useful new target for treating patients with CC.
TRIM11(含三联基序蛋白11)是一种E3泛素连接酶,最近被鉴定为恶性胶质瘤和肺癌中的一种癌基因。在本研究中,我们报告称,与配对的正常组织相比,结肠癌(CC)组织中TRIM11的表达增加,并且较高的TRIM11水平预示着CC患者的总生存期(OS)和无病生存期(DFS)较差。从机制上讲,我们表明miR-24-3p下调导致CC中TRIM11上调。我们还证明,TRIM11过表达促进CC细胞增殖和集落形成并抑制细胞凋亡,而使用CRISPR/Cas9介导的基因组编辑敲低TRIM11则抑制细胞增殖并诱导细胞凋亡。在体内沉默TRIM11可减少肿瘤生长。这些发现表明,TRIM11通过促进细胞增殖和抑制细胞凋亡促进CC进展,并且新的miR-24-3p/TRIM11轴可能是治疗CC患者的有用新靶点。