Wang Xiaolin, Shi Weiping, Shi Hongcan, Lu Shichun, Wang Kang, Sun Chao, He Jiansheng, Jin Weiguo, Lv Xiaoxia, Zou Hui, Shu Yusheng
Department of Thoracic Surgery, Northern Jiangsu People's Hospital and Clinical Medical College of Yangzhou University Yangzhou, No. 98 Nantong West Road, Yangzhou, 225001, People's Republic of China.
J Exp Clin Cancer Res. 2016 Jun 21;35(1):100. doi: 10.1186/s13046-016-0379-y.
Tripartite Motif Containing 11 (TRIM11), a member of TRIM proteins, is overexpressed in high-grade gliomas and plays an oncogenic function in glioma biology. However, little is known about the role of TRIM11 in lung cancer.
We analyzed TRIM11 mRNA expression in lung cancer tissues and adjacent non-neoplastic tissues by real-time PCR. We then explored the function of TRIM11 in lung cancer cells by small interfering RNA-mediated downregulation of this protein followed by analyses of cell proliferation, migration and invasion.
TRIM11 was highly expressed in lung cancer tissues and lung cancer cell lines. The higher expression of TRIM11 was correlated with the poorer prognosis of patients. Suppressing of TRIM11 expression in lung cancer cells with higher expression of TRIM11 (A549 and NCI-H446 cells) significantly reduced cell growth, motility and invasiveness. We further demonstrated that knockdown of TRIM11 affected the expression of cell proliferation-related proteins (Cyclin D1 and PCNA), and epithelial-mesenchymal transformation-related proteins (VEGF, MMP-2, MMP-9, Twist1, Snail and E-cadherin). The activity of ERK and PI3K/AKT was also suppressed in TRIM11 knocked down cells. Further experiments in lung cells with lower expression of TRIM11 (NCI-H460 and NCI-H1975 cells) with AKT inhibitor suggested that TRIM11 may promote cell motility and invasiveness through AKT pathway.
Our results indicate that TRIM11 acts as an oncogene in lung cancer through promoting cell growth, migration and invasion. Our findings may have important implication for the detection and treatment of lung cancer.
含三联基序蛋白11（TRIM11）是TRIM蛋白家族成员之一，在高级别胶质瘤中高表达，并在胶质瘤生物学中发挥致癌作用。然而，关于TRIM11在肺癌中的作用知之甚少。
我们通过实时PCR分析肺癌组织及相邻非肿瘤组织中TRIM11 mRNA的表达。然后，我们通过小干扰RNA介导下调该蛋白，分析细胞增殖、迁移和侵袭，探讨TRIM11在肺癌细胞中的功能。
TRIM11在肺癌组织和肺癌细胞系中高表达。TRIM11的高表达与患者较差的预后相关。在TRIM11高表达的肺癌细胞（A549和NCI-H446细胞）中抑制TRIM11表达，显著降低了细胞生长、运动性和侵袭性。我们进一步证明，敲低TRIM11影响细胞增殖相关蛋白（细胞周期蛋白D1和增殖细胞核抗原）以及上皮-间质转化相关蛋白（血管内皮生长因子、基质金属蛋白酶-2、基质金属蛋白酶-9、Twist1、Snail和E-钙黏蛋白）的表达。在敲低TRIM11的细胞中，细胞外调节蛋白激酶和磷脂酰肌醇-3激酶/蛋白激酶B的活性也受到抑制。用蛋白激酶B抑制剂对TRIM11低表达的肺癌细胞（NCI-H460和NCI-H1975细胞）进行的进一步实验表明，TRIM11可能通过蛋白激酶B途径促进细胞运动性和侵袭性。
我们的结果表明，TRIM11通过促进细胞生长、迁移和侵袭在肺癌中发挥癌基因作用。我们的发现可能对肺癌的检测和治疗具有重要意义。
