Overexpression of TRIM25 in Lung Cancer Regulates Tumor Cell Progression
Overexpression of TRIM25 in Lung Cancer Regulates Tumor Cell Progression
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DOI：
10.1177/1533034615595903
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发表时间：
2016-10-01
影响因子：
2.8
通讯作者：
Zhang, Hua
中科院分区：
文献类型：
--
作者：
Qin, Ying;Cui, He;Zhang, Hua
肺癌是全球癌症相关死亡的最常见原因之一。尽管近几十年来人们对肺癌的研究取得了很大的进展，但肺癌的形成机制仍不清楚。为了建立有效的治疗方法，必须确定肺癌过程中隐含的新靶点。含有三分基序的25与卵巢癌和乳腺癌有关，并被认为通过靶向细胞周期积极促进细胞生长。然而，含有三重基序的25是否在肺癌发展中具有功能仍然未知。在这项研究中，我们发现，在人肺癌组织中过表达的三重基序含有25。肺癌细胞中含三重基序的25的表达对于细胞增殖和迁移是重要的。敲除含三重基序的25在体外和体内均显著降低肺癌细胞的增殖，并在体外降低肺癌细胞的迁移。同时，含三联体基序的25沉默也增加了阿霉素的敏感性，并且通过敲低含三联体基序的25实现了阿霉素对肺癌细胞的死亡和凋亡的显著增加。我们还观察到，在人肺癌组织和肺癌细胞中，含有三重基序的25与p53和小鼠双微体2同源物（MDM 2）形成复合物，并且含有三重基序的25沉默增加了p53的表达。这些结果提供了证据表明，含三重基序的25可能通过促进肺癌细胞的增殖和迁移而参与肺癌的发病机制。因此，靶向含三重基序的25可能为肺癌提供潜在的治疗干预。
Lung cancer is one of the most common causes of cancer-related deaths worldwide. Although great efforts and progressions have been made in the study of the lung cancer in the recent decades, the mechanism of lung cancer formation remains elusive. To establish effective therapeutic methods, new targets implied in lung cancer processes have to be identified. Tripartite motif-containing 25 has been associated with ovarian and breast cancer and is thought to positively promote cell growth by targeting the cell cycle. However, whether tripartite motif-containing 25 has a function in lung cancer development remains unknown. In this study, we found that tripartite motif-containing 25 was overexpressed in human lung cancer tissues. Expression of tripartite motif-containing 25 in lung cancer cells is important for cell proliferation and migration. Knockdown of tripartite motif-containing 25 markedly reduced proliferation of lung cancer cells both in vitro and in vivo and reduced migration of lung cancer cells in vitro. Meanwhile, tripartite motif-containing 25 silencing also increased the sensitivity of doxorubicin and significantly increased death and apoptosis of lung cancer cells by doxorubicin were achieved with knockdown of tripartite motif-containing 25. We also observed that tripartite motif-containing 25 formed a complex with p53 and mouse double minute 2 homolog (MDM2) in both human lung cancer tissues and in lung cancer cells and tripartite motif-containing 25 silencing increased the expression of p53. These results provide evidence that tripartite motif-containing 25 contributes to the pathogenesis of lung cancer probably by promoting proliferation and migration of lung cancer cells. Therefore, targeting tripartite motif-containing 25 may provide a potential therapeutic intervention for lung cancer.