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DDX10 通过 U3 小核仁核糖核蛋白 IMP4 促进人肺癌增殖。

DDX10 promotes human lung carcinoma proliferation by U3 small nucleolar ribonucleoprotein IMP4.

机构信息

Department of Thoracic Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

出版信息

Thorac Cancer. 2021 Jun;12(12):1873-1880. doi: 10.1111/1759-7714.13976. Epub 2021 May 11.

Abstract

BACKGROUND

Lung cancer is a common tumor and a leading cause of death worldwide. DEAD/H box RNA helicases (DDX) include several family members which regulate mRNA translation in cancer cells. In this study, we demonstrated that DEAD/H box RNA helicase 10 (DDX10) was significantly upregulated in lung cancer tissues compared with adjacent nontumor tissues.

METHODS

DDX10 expression was knocked down with shRNA in order to investigate the impact on A549 lung cancer cell growth and related molecular mechanisms in vitro and in vivo. DDX10 expression in lung cancer was assessed using online databases and patient samples.

RESULTS

DDX10 knockdown significantly inhibited the proliferation of lung cancer cells in vitro and in vivo. Furthermore, the bioinformatic tool indicated the putative downstream protein U3 small nucleolar ribonucleoprotein 4 (IMP4). Our data showed a positive correlation between IMP4 and DDX10. We found that IMP4 overexpression could reverse the effect of DDX10 knockdown on the proliferation and apoptosis of A549 cells.

CONCLUSIONS

The findings of this study suggest that DDX10/IMP4 might be a novel target for lung cancer diagnosis and treatment.

摘要

背景

肺癌是一种常见的肿瘤,也是全球范围内导致死亡的主要原因。DEAD/H 盒 RNA 解旋酶(DDX)包括几个家族成员,它们在癌细胞中调节 mRNA 翻译。在这项研究中,我们证明与相邻非肿瘤组织相比,肺癌组织中 DEAD/H 盒 RNA 解旋酶 10(DDX10)的表达显著上调。

方法

利用 shRNA 敲低 DDX10,以研究其对体外和体内 A549 肺癌细胞生长的影响及相关分子机制。使用在线数据库和患者样本评估肺癌中 DDX10 的表达。

结果

DDX10 敲低显著抑制了肺癌细胞在体外和体内的增殖。此外,生物信息学工具预测了下游蛋白 U3 小核仁核糖核蛋白 4(IMP4)。我们的数据显示 IMP4 与 DDX10 之间存在正相关。我们发现,IMP4 过表达可以逆转 DDX10 敲低对 A549 细胞增殖和凋亡的影响。

结论

本研究结果表明,DDX10/IMP4 可能成为肺癌诊断和治疗的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64c/8201537/ec53e26b8c93/TCA-12-1873-g004.jpg

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