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miR-487a promotes progression of gastric cancer by targeting TIA1
Biochimie ( IF 3.9 ) Pub Date : 2018-08-23 , DOI: 10.1016/j.biochi.2018.08.006
Xuefeng Yang , Mingda Wang , Bohao Lin , Dongjie Yao , Jin Li , Xianchun Tang , Sanhua Li , Yun Liu , Rui Xie , Shouyang Yu

Gastric cancer (GC) is one of the most common malignancies as well as the third leading cause for cancer-related death. Molecular basis of GC are essential and critical for its therapeutic treatment, but still remain poorly understood. T-cell intracellular antigen-1 (TIA1) extensively involves in cancer progression, whereas its role and regulation mechanism in GC have not been revealed. In the present study, we found that TIA-1 protein level was down-regulated in GC tissues and TIA1 inhibited proliferation and promoted apoptosis of GC cells. Then, we used bioinformatics to predict miR-487a as the upstream regulator of TIA1 and we also observed an inverse correlation between miR-487a level and TIA-1 protein level in GC tissues. Next, we demonstrated that miR-487a directly targeted TIA1 via binding to its 3′-untranslated region. Furthermore, we investigated the role of miR-487a-TIA1 pathway in the growth of GC cells both in vitro and in vivo. The repression of TIA-1 by miR-487a promoted cell proliferation and suppressed cell apoptosis in vitro, and the knockdown of miR-487a had the opposite effects. Finally, we demonstrated that miR-487a promoted the development of gastric tumor growth in xenograft mice by targeting TIA-1. These effects could be partially reversed by restoring the expression of TIA-1. Overall, our results reveal that TIA1 is a tumor suppressor gene and is directly regulated by miR-487a in GC, which may offer new therapeutic targets for GC treatment.



中文翻译:

miR-487a通过靶向TIA1促进胃癌的进展

胃癌(GC)是最常见的恶性肿瘤之一,也是与癌症相关的死亡的第三大主要原因。GC的分子基础对其治疗至关重要,但仍知之甚少。T细胞细胞内抗原1(TIA1)广泛参与癌症的进展,而其在GC中的作用和调控机制尚未揭示。在本研究中,我们发现TIA-1蛋白水平在GC组织中下调,而TIA1抑制了GC细胞的增殖并促进了其凋亡。然后,我们使用生物信息学预测了miR-487a作为TIA1的上游调节剂,并且还观察到了GC组织中miR-487a水平与TIA-1蛋白水平呈负相关。接下来,我们证明了miR-487a通过与其3'-非翻译区结合直接靶向TIA1。此外,体外体内。miR-487a对TIA-1的抑制在体外可促进细胞增殖并抑制细胞凋亡,而miR-487a的敲低则具有相反的作用。最后,我们证明了miR-487a通过靶向TIA-1促进了异种移植小鼠胃肿瘤生长的发展。通过恢复TIA-1的表达,可以部分逆转这些影响。总体而言,我们的结果表明TIA1是一种抑癌基因,在GC中直接受miR-487a调控,这可能为GC治疗提供新的治疗靶点。

更新日期:2018-08-23
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